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Erschienen in: Endocrine 3/2018

02.05.2018 | Review

The emerging role of aldosterone/mineralocorticoid receptors in the pathogenesis of erectile dysfunction

verfasst von: Fei Wu, Yun Lin, Qingyong Liu

Erschienen in: Endocrine | Ausgabe 3/2018

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Abstract

Purpose

Aldosterone is an old hormone that has been discovered for more than fifty years. The clinical application of its receptors' inhibitors, especially spirolactone, has benifited patients for decades worldwide. In this review, we briefly summarized the molecular mechanism of aldosterone/mineralocorticoid receptors (Ald-MRs) signaling in cardiovascular diseases and its emerging role in erectile dysfunction.

Methods

We searched PubMed, Web of Science, and Scopus for manuscripts published prior to December 2017 using key words " aldosterone " AND " erectile dysfunction " OR " cardiovascular disease " OR " mineralocorticoid receptors ". Related literature and clinical perspectives were collated, summarized and discussed in this review.

Results

The increase of reactive oxygen species production, inhibition of endothelial nitric oxide synthase system, and induction of inflammation are ubiquitous in vascular endothelial cells or vascular smooth muscle cells after the activation of Ald-MRs pathway. In addition, in cardiovascular diseases with over-active Ald-MRs signaling, MRs blockade could reverse the injury and improve the prognosis. Notably, multiple studies have correlated aldosterone and MRs to the pathogenesis of erectile function, while the mechanism is largely unperfectly identified.

Conclusion

In conclusion, we summarize the current evidence to highlight the potential role of aldosterone in erectile dysfunction and provide critical insights into the treatment of the disease.
Literatur
1.
Zurück zum Zitat B.C. Rossier, M.E. Baker, R.A. Studerr, Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited. Physiol. Rev. 95, 297–340 (2015)PubMedCrossRef B.C. Rossier, M.E. Baker, R.A. Studerr, Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited. Physiol. Rev. 95, 297–340 (2015)PubMedCrossRef
2.
Zurück zum Zitat P.J. Fuller, Y. Yao, J. Yang, M.J. Young, Mechanisms of ligand specificity of the mineralocorticoid receptor. J. Endocrinol. 213, 15–24 (2012)PubMedCrossRef P.J. Fuller, Y. Yao, J. Yang, M.J. Young, Mechanisms of ligand specificity of the mineralocorticoid receptor. J. Endocrinol. 213, 15–24 (2012)PubMedCrossRef
3.
Zurück zum Zitat F. Jaisser, N. Farman, Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology. Pharmacol. Rev. 68, 49–75 (2016)PubMedCrossRef F. Jaisser, N. Farman, Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology. Pharmacol. Rev. 68, 49–75 (2016)PubMedCrossRef
4.
Zurück zum Zitat J.W. Funder, The role of aldosterone and mineralocorticoid receptors in cardiovascular disease. Am. J. Cardiovasc. Drugs 7, 151–157 (2007)PubMedCrossRef J.W. Funder, The role of aldosterone and mineralocorticoid receptors in cardiovascular disease. Am. J. Cardiovasc. Drugs 7, 151–157 (2007)PubMedCrossRef
5.
Zurück zum Zitat M. Heinrich, J.M. Prieto, Diet and healthy ageing 2100: will we globalise local knowledge systems? Ageing Res. Rev. 7, 249–274 (2008)PubMedCrossRef M. Heinrich, J.M. Prieto, Diet and healthy ageing 2100: will we globalise local knowledge systems? Ageing Res. Rev. 7, 249–274 (2008)PubMedCrossRef
6.
7.
Zurück zum Zitat NIH Consensus Conference. Impotence. NIH consensus development panel on impotence. JAMA 270, 83–90 (1993)CrossRef NIH Consensus Conference. Impotence. NIH consensus development panel on impotence. JAMA 270, 83–90 (1993)CrossRef
8.
Zurück zum Zitat I.A. Ayta, J.B. McKinlay, R.J. Krane, The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 84, 50–56 (1999)PubMedCrossRef I.A. Ayta, J.B. McKinlay, R.J. Krane, The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 84, 50–56 (1999)PubMedCrossRef
9.
Zurück zum Zitat S.D. Cohen, The challenge of erectile dysfunction management in the young man. Curr. Urol. Rep. 16, 84 (2015)PubMedCrossRef S.D. Cohen, The challenge of erectile dysfunction management in the young man. Curr. Urol. Rep. 16, 84 (2015)PubMedCrossRef
10.
Zurück zum Zitat A.D. Seftel, P. Sun, R. Swindle, The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J. Urol. 171, 2341–2345 (2004)PubMedCrossRef A.D. Seftel, P. Sun, R. Swindle, The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J. Urol. 171, 2341–2345 (2004)PubMedCrossRef
11.
Zurück zum Zitat R.W. Lewis, K.S. Fugl-Meyer, G. Corona, R.D. Hayes, E.O. Laumann, E.D. Moreira Jr., A.H. Rellini, T. Segraves, Definitions/epidemiology/risk factors for sexual dysfunction. J. Sex. Med. 7, 1598–1607 (2010)PubMedCrossRef R.W. Lewis, K.S. Fugl-Meyer, G. Corona, R.D. Hayes, E.O. Laumann, E.D. Moreira Jr., A.H. Rellini, T. Segraves, Definitions/epidemiology/risk factors for sexual dysfunction. J. Sex. Med. 7, 1598–1607 (2010)PubMedCrossRef
12.
Zurück zum Zitat C.G. Bacon, M.A. Mittleman, I. Kawachi, E. Giovannucci, D.B. Glasser, E.B. Rimm, Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann. Intern. Med. 139, 161–168 (2003)PubMedCrossRef C.G. Bacon, M.A. Mittleman, I. Kawachi, E. Giovannucci, D.B. Glasser, E.B. Rimm, Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann. Intern. Med. 139, 161–168 (2003)PubMedCrossRef
13.
Zurück zum Zitat Y.C. Huang, C.C. Chin, C.S. Chen, A.W. Shindel, D.R. Ho, C.S. Lin, C.S. Shi, Chronic cigarette smoking impairs erectile function through increased oxidative stress and apoptosis, decreased nNOS, endothelial and smooth muscle contents in a rat model. PLoS ONE 10, e0140728 (2015)PubMedPubMedCentralCrossRef Y.C. Huang, C.C. Chin, C.S. Chen, A.W. Shindel, D.R. Ho, C.S. Lin, C.S. Shi, Chronic cigarette smoking impairs erectile function through increased oxidative stress and apoptosis, decreased nNOS, endothelial and smooth muscle contents in a rat model. PLoS ONE 10, e0140728 (2015)PubMedPubMedCentralCrossRef
14.
Zurück zum Zitat M.J. Pagano, A. De Fazio, A. Levy, A. RoyChoudhury, P.J. Stahl, Age, body mass index, and frequency of sexual activity are independent predictors of testosterone deficiency in men with erectile dysfunction. Urology 90, 112–118 (2016)PubMedCrossRef M.J. Pagano, A. De Fazio, A. Levy, A. RoyChoudhury, P.J. Stahl, Age, body mass index, and frequency of sexual activity are independent predictors of testosterone deficiency in men with erectile dysfunction. Urology 90, 112–118 (2016)PubMedCrossRef
15.
Zurück zum Zitat J. Buvat, M. Maggi, L. Gooren, A.T. Guay, J. Kaufman, A. Morgentaler, C. Schulman, H.M. Tan, L.O. Torres, A. Yassin, M. Zitzmann, Endocrine aspects of male sexual dysfunctions. J. Sex. Med. 7, 1627–1656 (2010)PubMedCrossRef J. Buvat, M. Maggi, L. Gooren, A.T. Guay, J. Kaufman, A. Morgentaler, C. Schulman, H.M. Tan, L.O. Torres, A. Yassin, M. Zitzmann, Endocrine aspects of male sexual dysfunctions. J. Sex. Med. 7, 1627–1656 (2010)PubMedCrossRef
16.
Zurück zum Zitat M. De Rosa, S. Zarrilli, G. Vitale, C. Di Somma, F. Orio, L. Tauchmanova, G. Lombardi, A. Colao, Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence. J. Clin. Endocrinol. Metab. 89, 621–625 (2004)PubMedCrossRef M. De Rosa, S. Zarrilli, G. Vitale, C. Di Somma, F. Orio, L. Tauchmanova, G. Lombardi, A. Colao, Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence. J. Clin. Endocrinol. Metab. 89, 621–625 (2004)PubMedCrossRef
17.
Zurück zum Zitat W.J. Reiter, A. Pycha, G. Schatzl, A. Pokorny, D.M. Gruber, J.C. Huber, M. Marberger, Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology 53, 590–594; discussion 594–595 (1999). W.J. Reiter, A. Pycha, G. Schatzl, A. Pokorny, D.M. Gruber, J.C. Huber, M. Marberger, Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology 53, 590–594; discussion 594–595 (1999).
18.
Zurück zum Zitat A. Morales, A. Black, L. Emerson, J. Barkin, I. Kuzmarov, A. Day, Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency. Aging Male. 12, 104–112 (2009)PubMedCrossRef A. Morales, A. Black, L. Emerson, J. Barkin, I. Kuzmarov, A. Day, Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency. Aging Male. 12, 104–112 (2009)PubMedCrossRef
19.
Zurück zum Zitat G.E. Krassas, K. Tziomalos, F. Papadopoulou, N. Pontikides, P. Perros, Erectile dysfunction in patients with hyper- and hypothyroidism: how common and should we treat? J. Clin. Endocrinol. Metab. 93, 1815–1819 (2008)PubMedCrossRef G.E. Krassas, K. Tziomalos, F. Papadopoulou, N. Pontikides, P. Perros, Erectile dysfunction in patients with hyper- and hypothyroidism: how common and should we treat? J. Clin. Endocrinol. Metab. 93, 1815–1819 (2008)PubMedCrossRef
20.
Zurück zum Zitat A. Veronelli, A. Masu, R. Ranieri, C. Rognoni, M. Laneri, A.E. Pontiroli, Prevalence of erectile dysfunction in thyroid disorders: comparison with control subjects and with obese and diabetic patients. Int. J. Impot. Res. 18, 111–114 (2006)PubMedCrossRef A. Veronelli, A. Masu, R. Ranieri, C. Rognoni, M. Laneri, A.E. Pontiroli, Prevalence of erectile dysfunction in thyroid disorders: comparison with control subjects and with obese and diabetic patients. Int. J. Impot. Res. 18, 111–114 (2006)PubMedCrossRef
21.
Zurück zum Zitat M. Caprio, C. Mammi, I.Z. Jaffe, M.C. Zennaro, A. Aversa, M.E. Mendelsohn, A. Fabbri, G.M. Rosano, The mineralocorticoid receptor in endothelial physiology and disease: novel concepts in the understanding of erectile dysfunction. Curr. Pharm. Des. 14, 3749–3757 (2008)PubMedCrossRef M. Caprio, C. Mammi, I.Z. Jaffe, M.C. Zennaro, A. Aversa, M.E. Mendelsohn, A. Fabbri, G.M. Rosano, The mineralocorticoid receptor in endothelial physiology and disease: novel concepts in the understanding of erectile dysfunction. Curr. Pharm. Des. 14, 3749–3757 (2008)PubMedCrossRef
22.
Zurück zum Zitat T. Kishimoto, T. Fukawa, K. Yamaguchi, Y. Yamamoto, H. Nakatsuji, H. Izaki, M. Takahashi, T. Fukumori, H.O. Kanayama, Mineralocorticoid receptor expression in human penile corpus cavernosum. J. Med. Invest. 60, 21–26 (2013)PubMedCrossRef T. Kishimoto, T. Fukawa, K. Yamaguchi, Y. Yamamoto, H. Nakatsuji, H. Izaki, M. Takahashi, T. Fukumori, H.O. Kanayama, Mineralocorticoid receptor expression in human penile corpus cavernosum. J. Med. Invest. 60, 21–26 (2013)PubMedCrossRef
23.
Zurück zum Zitat H. Muguruma, Y. Kawanishi, H. Sugiyama, J. Kagawa, S. Tanimoto, M. Yamanaka, K. Kojima, H. Anzai, A. Numata, T. Kishimoto, H.O. Kanayama, Effect of aldosterone on isolated human penile corpus cavernosum tissue. BJU Int. 102, 500–503 (2008)PubMedCrossRef H. Muguruma, Y. Kawanishi, H. Sugiyama, J. Kagawa, S. Tanimoto, M. Yamanaka, K. Kojima, H. Anzai, A. Numata, T. Kishimoto, H.O. Kanayama, Effect of aldosterone on isolated human penile corpus cavernosum tissue. BJU Int. 102, 500–503 (2008)PubMedCrossRef
24.
Zurück zum Zitat F. Wu, S. Mao, T. Yu, H. Jiang, Q. Ding, G. Xu, Elevated plasma aldosterone is an independent risk factor for erectile dysfunction in men. World J. Urol. 34, 999–1007 (2016).PubMedCrossRef F. Wu, S. Mao, T. Yu, H. Jiang, Q. Ding, G. Xu, Elevated plasma aldosterone is an independent risk factor for erectile dysfunction in men. World J. Urol. 34, 999–1007 (2016).PubMedCrossRef
25.
Zurück zum Zitat C. Hellal-Levy, J. Fagart, A. Souque, M.E. Rafestin-Oblin, Mechanistic aspects of mineralocorticoid receptor activation. Kidney Int. 57, 1250–1255 (2000)PubMedCrossRef C. Hellal-Levy, J. Fagart, A. Souque, M.E. Rafestin-Oblin, Mechanistic aspects of mineralocorticoid receptor activation. Kidney Int. 57, 1250–1255 (2000)PubMedCrossRef
26.
Zurück zum Zitat M. Bader, Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu. Rev. Pharmacol. Toxicol. 50, 439–465 (2010)PubMedCrossRef M. Bader, Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu. Rev. Pharmacol. Toxicol. 50, 439–465 (2010)PubMedCrossRef
27.
Zurück zum Zitat M.D. Taves, C.E. Gomez-Sanchez, K.K. Soma, Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am. J. Physiol. Endocrinol. Metab. 301, E11–E24 (2011)PubMedPubMedCentralCrossRef M.D. Taves, C.E. Gomez-Sanchez, K.K. Soma, Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am. J. Physiol. Endocrinol. Metab. 301, E11–E24 (2011)PubMedPubMedCentralCrossRef
28.
Zurück zum Zitat L.G. Palmer, G. Frindt, Na+and K+transport by the renal connecting tubule. Curr. Opin. Nephrol. Hypertens. 16, 477–483 (2007)PubMedCrossRef L.G. Palmer, G. Frindt, Na+and K+transport by the renal connecting tubule. Curr. Opin. Nephrol. Hypertens. 16, 477–483 (2007)PubMedCrossRef
29.
Zurück zum Zitat R. Soundararajan, D. Melters, I.C. Shih, J. Wang, D. Pearce, Epithelial sodium channel regulated by differential composition of a signaling complex. Proc. Natl Acad. Sci. USA 106, 7804–7809 (2009)PubMedCrossRef R. Soundararajan, D. Melters, I.C. Shih, J. Wang, D. Pearce, Epithelial sodium channel regulated by differential composition of a signaling complex. Proc. Natl Acad. Sci. USA 106, 7804–7809 (2009)PubMedCrossRef
30.
Zurück zum Zitat R. Soundararajan, T. Ziera, E. Koo, K. Ling, J. Wang, S.A. Borden, D. Pearce, Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex. J. Biol. Chem. 287, 33014–33025 (2012)PubMedPubMedCentralCrossRef R. Soundararajan, T. Ziera, E. Koo, K. Ling, J. Wang, S.A. Borden, D. Pearce, Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex. J. Biol. Chem. 287, 33014–33025 (2012)PubMedPubMedCentralCrossRef
31.
32.
Zurück zum Zitat D. Pearce, R. Soundararajan, C. Trimpert, O.B. Kashlan, P.M. Deen, D.E. Kohan, Collecting duct principal cell transport processes and their regulation. Clin. J. Am. Soc. Nephrol. 10, 135–146 (2015)PubMedCrossRef D. Pearce, R. Soundararajan, C. Trimpert, O.B. Kashlan, P.M. Deen, D.E. Kohan, Collecting duct principal cell transport processes and their regulation. Clin. J. Am. Soc. Nephrol. 10, 135–146 (2015)PubMedCrossRef
33.
Zurück zum Zitat F. Verrey, E. Schaerer, P. Zoerkler, M.P. Paccolat, K. Geering, J.P. Kraehenbuhl, B.C. Rossier, Regulation by aldosterone of Na+,K+-ATPase mRNAs, protein synthesis, and sodium transport in cultured kidney cells. J. Cell Biol. 104, 1231–1237 (1987)PubMedCrossRef F. Verrey, E. Schaerer, P. Zoerkler, M.P. Paccolat, K. Geering, J.P. Kraehenbuhl, B.C. Rossier, Regulation by aldosterone of Na+,K+-ATPase mRNAs, protein synthesis, and sodium transport in cultured kidney cells. J. Cell Biol. 104, 1231–1237 (1987)PubMedCrossRef
34.
Zurück zum Zitat A. Odermatt, D.V. Kratschmar, Tissue-specific modulation of mineralocorticoid receptor function by 11beta-hydroxysteroid dehydrogenases: an overview. Mol. Cell. Endocrinol. 350, 168–186 (2012)PubMedCrossRef A. Odermatt, D.V. Kratschmar, Tissue-specific modulation of mineralocorticoid receptor function by 11beta-hydroxysteroid dehydrogenases: an overview. Mol. Cell. Endocrinol. 350, 168–186 (2012)PubMedCrossRef
35.
Zurück zum Zitat N. Farman, M.E. Rafestin-Oblin, Multiple aspects of mineralocorticoid selectivity. Am. J. Physiol. Ren. Physiol. 280, F181–F192 (2001)CrossRef N. Farman, M.E. Rafestin-Oblin, Multiple aspects of mineralocorticoid selectivity. Am. J. Physiol. Ren. Physiol. 280, F181–F192 (2001)CrossRef
36.
Zurück zum Zitat J. Huyet, G.M. Pinon, M.R. Fay, M.E. Rafestin-Oblin, J. Fagart, Structural determinants of ligand binding to the mineralocorticoid receptor. Mol. Cell. Endocrinol. 350, 187–195 (2012)PubMedCrossRef J. Huyet, G.M. Pinon, M.R. Fay, M.E. Rafestin-Oblin, J. Fagart, Structural determinants of ligand binding to the mineralocorticoid receptor. Mol. Cell. Endocrinol. 350, 187–195 (2012)PubMedCrossRef
37.
Zurück zum Zitat M. Caprio, B.G. Newfell, A. la Sala, W. Baur, A. Fabbri, G. Rosano, M.E. Mendelsohn, I.Z. Jaffe, Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ. Res. 102, 1359–1367 (2008)PubMedPubMedCentralCrossRef M. Caprio, B.G. Newfell, A. la Sala, W. Baur, A. Fabbri, G. Rosano, M.E. Mendelsohn, I.Z. Jaffe, Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ. Res. 102, 1359–1367 (2008)PubMedPubMedCentralCrossRef
38.
Zurück zum Zitat J.W. Funder, P.T. Pearce, R. Smith, A.I. Smith, Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242, 583–585 (1988)PubMedCrossRef J.W. Funder, P.T. Pearce, R. Smith, A.I. Smith, Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242, 583–585 (1988)PubMedCrossRef
39.
Zurück zum Zitat L.A. Calo, F. Zaghetto, E. Pagnin, P.A. Davis, P. De Mozzi, P. Sartorato, G. Martire, C. Fiore, D. Armanini, Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 andp22(phox) in human mononuclear leukocytes. J. Clin. Endocrinol. Metab. 89, 1973–1976 (2004)PubMedCrossRef L.A. Calo, F. Zaghetto, E. Pagnin, P.A. Davis, P. De Mozzi, P. Sartorato, G. Martire, C. Fiore, D. Armanini, Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 andp22(phox) in human mononuclear leukocytes. J. Clin. Endocrinol. Metab. 89, 1973–1976 (2004)PubMedCrossRef
40.
Zurück zum Zitat A. Sato, J.W. Funder, High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinology 137, 4145–4153 (1996)PubMedCrossRef A. Sato, J.W. Funder, High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinology 137, 4145–4153 (1996)PubMedCrossRef
41.
Zurück zum Zitat M. Lombes, M.E. Oblin, J.M. Gasc, E.E. Baulieu, N. Farman, J.P. Bonvalet, Immunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor. Circ. Res. 71, 503–510 (1992)PubMedCrossRef M. Lombes, M.E. Oblin, J.M. Gasc, E.E. Baulieu, N. Farman, J.P. Bonvalet, Immunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor. Circ. Res. 71, 503–510 (1992)PubMedCrossRef
42.
Zurück zum Zitat Q.N. Dinh, T.V. Arumugam, M.J. Young, G.R. Drummond, C.G. Sobey, S. Chrissobolis, Aldosterone and the mineralocorticoid receptor in the cerebral circulation and stroke. Exp. Transl. Stroke Med. 4, 21 (2012)PubMedPubMedCentralCrossRef Q.N. Dinh, T.V. Arumugam, M.J. Young, G.R. Drummond, C.G. Sobey, S. Chrissobolis, Aldosterone and the mineralocorticoid receptor in the cerebral circulation and stroke. Exp. Transl. Stroke Med. 4, 21 (2012)PubMedPubMedCentralCrossRef
43.
Zurück zum Zitat C.E. Gomez-Sanchez, M.Y. Zhou, E.N. Cozza, H. Morita, M.F. Foecking, E.P. Gomez-Sanchez, Aldosterone biosynthesis in the rat brain. Endocrinology 138, 3369–3373 (1997)PubMedCrossRef C.E. Gomez-Sanchez, M.Y. Zhou, E.N. Cozza, H. Morita, M.F. Foecking, E.P. Gomez-Sanchez, Aldosterone biosynthesis in the rat brain. Endocrinology 138, 3369–3373 (1997)PubMedCrossRef
44.
Zurück zum Zitat Q.N. Dinh, M.J. Young, M.A. Evans, G.R. Drummond, C.G. Sobey, S. Chrissobolis, Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor. Brain Res. 1637, 146–153 (2016)PubMedCrossRef Q.N. Dinh, M.J. Young, M.A. Evans, G.R. Drummond, C.G. Sobey, S. Chrissobolis, Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor. Brain Res. 1637, 146–153 (2016)PubMedCrossRef
45.
Zurück zum Zitat C.T. Tsai, F.T. Chiang, C.D. Tseng, J.J. Hwang, K.T. Kuo, C.K. Wu, C.C. Yu, Y.C. Wang, L.P. Lai, J.L. Lin, Increased expression of mineralocorticoid receptor in human atrial fibrillation and a cellular model of atrial fibrillation. J. Am. Coll. Cardiol. 55, 758–770 (2010)PubMedCrossRef C.T. Tsai, F.T. Chiang, C.D. Tseng, J.J. Hwang, K.T. Kuo, C.K. Wu, C.C. Yu, Y.C. Wang, L.P. Lai, J.L. Lin, Increased expression of mineralocorticoid receptor in human atrial fibrillation and a cellular model of atrial fibrillation. J. Am. Coll. Cardiol. 55, 758–770 (2010)PubMedCrossRef
46.
Zurück zum Zitat B.J. He, M.L. Joiner, M.V. Singh, E.D. Luczak, P.D. Swaminathan, O.M. Koval, W. Kutschke, C. Allamargot, J. Yang, X. Guan, K. Zimmerman, I.M. Grumbach, R.M. Weiss, D.R. Spitz, C.D. Sigmund, W.M. Blankesteijn, S. Heymans, P.J. Mohler, M.E. Anderson, Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat. Med. 17, 1610–1618 (2011)PubMedPubMedCentralCrossRef B.J. He, M.L. Joiner, M.V. Singh, E.D. Luczak, P.D. Swaminathan, O.M. Koval, W. Kutschke, C. Allamargot, J. Yang, X. Guan, K. Zimmerman, I.M. Grumbach, R.M. Weiss, D.R. Spitz, C.D. Sigmund, W.M. Blankesteijn, S. Heymans, P.J. Mohler, M.E. Anderson, Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nat. Med. 17, 1610–1618 (2011)PubMedPubMedCentralCrossRef
47.
Zurück zum Zitat N. Lalevee, M.C. Rebsamen, S. Barrere-Lemaire, E. Perrier, J. Nargeot, J.P. Benitah, M.F. Rossier, Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes. Cardiovasc. Res. 67, 216–224 (2005)PubMedCrossRef N. Lalevee, M.C. Rebsamen, S. Barrere-Lemaire, E. Perrier, J. Nargeot, J.P. Benitah, M.F. Rossier, Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes. Cardiovasc. Res. 67, 216–224 (2005)PubMedCrossRef
48.
Zurück zum Zitat J.G. Burniston, A. Saini, L.B. Tan, D.F. Goldspink, Aldosterone induces myocyte apoptosis in the heart and skeletal muscles of rats in vivo. J. Mol. Cell. Cardiol. 39, 395–399 (2005)PubMedCrossRef J.G. Burniston, A. Saini, L.B. Tan, D.F. Goldspink, Aldosterone induces myocyte apoptosis in the heart and skeletal muscles of rats in vivo. J. Mol. Cell. Cardiol. 39, 395–399 (2005)PubMedCrossRef
49.
Zurück zum Zitat P. Du Bois, C. Pablo Tortola, D. Lodka, M. Kny, F. Schmidt, K. Song, S. Schmidt, R. Bassel-Duby, E.N. Olson, J. Fielitz, Angiotensin II induces skeletal muscle atrophy by activating TFEB-mediated MuRF1 expression. Circ. Res. 117, 424–436 (2015)PubMedPubMedCentralCrossRef P. Du Bois, C. Pablo Tortola, D. Lodka, M. Kny, F. Schmidt, K. Song, S. Schmidt, R. Bassel-Duby, E.N. Olson, J. Fielitz, Angiotensin II induces skeletal muscle atrophy by activating TFEB-mediated MuRF1 expression. Circ. Res. 117, 424–436 (2015)PubMedPubMedCentralCrossRef
50.
Zurück zum Zitat A.P. Johnston, J. Baker, M. De Lisio, G. Parise, Skeletal muscle myoblasts possess a stretch-responsive local angiotensin signalling system. J. Renin. Angiotensin. Aldosterone. Syst. 12, 75–84 (2011)PubMedCrossRef A.P. Johnston, J. Baker, M. De Lisio, G. Parise, Skeletal muscle myoblasts possess a stretch-responsive local angiotensin signalling system. J. Renin. Angiotensin. Aldosterone. Syst. 12, 75–84 (2011)PubMedCrossRef
51.
Zurück zum Zitat A. Bergmann, C. Eulenberg, M. Wellner, S. Rolle, F. Luft, R. Kettritz, Aldosterone abrogates nuclear factor kappaB-mediated tumor necrosis factor alpha production in human neutrophils via the mineralocorticoid receptor. Hypertension 55, 370–379 (2010)PubMedCrossRef A. Bergmann, C. Eulenberg, M. Wellner, S. Rolle, F. Luft, R. Kettritz, Aldosterone abrogates nuclear factor kappaB-mediated tumor necrosis factor alpha production in human neutrophils via the mineralocorticoid receptor. Hypertension 55, 370–379 (2010)PubMedCrossRef
52.
Zurück zum Zitat A. Vinh, W. Chen, Y. Blinder, D. Weiss, W.R. Taylor, J.J. Goronzy, C.M. Weyand, D.G. Harrison, T.J. Guzik, Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation 122, 2529–2537 (2010)PubMedPubMedCentralCrossRef A. Vinh, W. Chen, Y. Blinder, D. Weiss, W.R. Taylor, J.J. Goronzy, C.M. Weyand, D.G. Harrison, T.J. Guzik, Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation 122, 2529–2537 (2010)PubMedPubMedCentralCrossRef
53.
Zurück zum Zitat T.J. Guzik, N.E. Hoch, K.A. Brown, L.A. McCann, A. Rahman, S. Dikalov, J. Goronzy, C. Weyand, D.G. Harrison, Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J. Exp. Med. 204, 2449–2460 (2007)PubMedPubMedCentralCrossRef T.J. Guzik, N.E. Hoch, K.A. Brown, L.A. McCann, A. Rahman, S. Dikalov, J. Goronzy, C. Weyand, D.G. Harrison, Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J. Exp. Med. 204, 2449–2460 (2007)PubMedPubMedCentralCrossRef
54.
Zurück zum Zitat A.A. Herrada, F.J. Contreras, N.P. Marini, C.A. Amador, P.A. Gonzalez, C.M. Cortes, C.A. Riedel, C.A. Carvajal, F. Figueroa, L.F. Michea, C.E. Fardella, A.M. Kalergis, Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. J. Immunol. 184, 191–202 (2010)PubMedCrossRef A.A. Herrada, F.J. Contreras, N.P. Marini, C.A. Amador, P.A. Gonzalez, C.M. Cortes, C.A. Riedel, C.A. Carvajal, F. Figueroa, L.F. Michea, C.E. Fardella, A.M. Kalergis, Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. J. Immunol. 184, 191–202 (2010)PubMedCrossRef
55.
Zurück zum Zitat D.A. Kasal, T. Barhoumi, M.W. Li, N. Yamamoto, E. Zdanovich, A. Rehman, M.F. Neves, P. Laurant, P. Paradis, E.L. Schiffrin, T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension 59, 324–330 (2012)PubMedCrossRef D.A. Kasal, T. Barhoumi, M.W. Li, N. Yamamoto, E. Zdanovich, A. Rehman, M.F. Neves, P. Laurant, P. Paradis, E.L. Schiffrin, T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension 59, 324–330 (2012)PubMedCrossRef
56.
Zurück zum Zitat M. Lombes, N. Farman, J.P. Bonvalet, M.C. Zennaro, Identification and role of aldosterone receptors in the cardiovascular system. Ann. Endocrinol. 61, 41–46 (2000) M. Lombes, N. Farman, J.P. Bonvalet, M.C. Zennaro, Identification and role of aldosterone receptors in the cardiovascular system. Ann. Endocrinol. 61, 41–46 (2000)
57.
Zurück zum Zitat Q. Pu, M.F. Neves, A. Virdis, R.M. Touyz, E.L. Schiffrin, Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 42, 49–55 (2003)PubMedCrossRef Q. Pu, M.F. Neves, A. Virdis, R.M. Touyz, E.L. Schiffrin, Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 42, 49–55 (2003)PubMedCrossRef
58.
Zurück zum Zitat R. Rocha, A.E. Rudolph, G.E. Frierdich, D.A. Nachowiak, B.K. Kekec, E.A. Blomme, E.G. McMahon, J.A. Delyani, Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am. J. Physiol. Heart Circ. Physiol. 283, H1802–H1810 (2002)PubMedCrossRef R. Rocha, A.E. Rudolph, G.E. Frierdich, D.A. Nachowiak, B.K. Kekec, E.A. Blomme, E.G. McMahon, J.A. Delyani, Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am. J. Physiol. Heart Circ. Physiol. 283, H1802–H1810 (2002)PubMedCrossRef
59.
Zurück zum Zitat Y. Sun, J. Zhang, L. Lu, S.S. Chen, M.T. Quinn, K.T. Weber, Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am. J. Pathol. 161, 1773–1781 (2002)PubMedPubMedCentralCrossRef Y. Sun, J. Zhang, L. Lu, S.S. Chen, M.T. Quinn, K.T. Weber, Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am. J. Pathol. 161, 1773–1781 (2002)PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat I.Z. Jaffe, M.E. Mendelsohn, Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ. Res. 96, 643–650 (2005)PubMedCrossRef I.Z. Jaffe, M.E. Mendelsohn, Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ. Res. 96, 643–650 (2005)PubMedCrossRef
61.
Zurück zum Zitat I.Z. Jaffe, Y. Tintut, B.G. Newfell, L.L. Demer, M.E. Mendelsohn, Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler. Thromb. Vasc. Biol. 27, 799–805 (2007)PubMedCrossRef I.Z. Jaffe, Y. Tintut, B.G. Newfell, L.L. Demer, M.E. Mendelsohn, Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler. Thromb. Vasc. Biol. 27, 799–805 (2007)PubMedCrossRef
62.
Zurück zum Zitat B.J. Waddell, S. Hisheh, Z.S. Krozowski, P.J. Burton, Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male reproductive tract. Endocrinology 144, 3101–3106 (2003)PubMedCrossRef B.J. Waddell, S. Hisheh, Z.S. Krozowski, P.J. Burton, Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male reproductive tract. Endocrinology 144, 3101–3106 (2003)PubMedCrossRef
63.
Zurück zum Zitat F. Wu, Z.Q. Xiong, S.H. Mao, J.M. Hu, J.Q. Wang, H.W. Jiang, Q. Ding, Aldosterone induces inflammatory cytokines in penile corpus cavernosum by activating the NF-kappaB pathway. Asian J. Androl. 20, 24–29 (2018)PubMedCrossRef F. Wu, Z.Q. Xiong, S.H. Mao, J.M. Hu, J.Q. Wang, H.W. Jiang, Q. Ding, Aldosterone induces inflammatory cytokines in penile corpus cavernosum by activating the NF-kappaB pathway. Asian J. Androl. 20, 24–29 (2018)PubMedCrossRef
64.
Zurück zum Zitat R.F. Reilly, D.H. Ellison, Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol. Rev. 80, 277–313 (2000)PubMedCrossRef R.F. Reilly, D.H. Ellison, Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol. Rev. 80, 277–313 (2000)PubMedCrossRef
65.
Zurück zum Zitat M.K. Rude, T.A. Duhaney, G.M. Kuster, S. Judge, J. Heo, W.S. Colucci, D.A. Siwik, F. Sam, Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension 46, 555–561 (2005)PubMedCrossRef M.K. Rude, T.A. Duhaney, G.M. Kuster, S. Judge, J. Heo, W.S. Colucci, D.A. Siwik, F. Sam, Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension 46, 555–561 (2005)PubMedCrossRef
66.
Zurück zum Zitat S. Johar, A.C. Cave, A. Narayanapanicker, D.J. Grieve, A.M. Shah, Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. Faseb. J. 20, 1546–1548 (2006)PubMedCrossRef S. Johar, A.C. Cave, A. Narayanapanicker, D.J. Grieve, A.M. Shah, Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. Faseb. J. 20, 1546–1548 (2006)PubMedCrossRef
67.
Zurück zum Zitat S. Keidar, M. Kaplan, E. Pavlotzky, R. Coleman, T. Hayek, S. Hamoud, M. Aviram, Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation 109, 2213–2220 (2004)PubMedCrossRef S. Keidar, M. Kaplan, E. Pavlotzky, R. Coleman, T. Hayek, S. Hamoud, M. Aviram, Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation 109, 2213–2220 (2004)PubMedCrossRef
68.
Zurück zum Zitat F. Iwashima, T. Yoshimoto, I. Minami, M. Sakurada, Y. Hirono, Y. Hirata, Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. Endocrinology 149, 1009–1014 (2008)PubMedCrossRef F. Iwashima, T. Yoshimoto, I. Minami, M. Sakurada, Y. Hirono, Y. Hirata, Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. Endocrinology 149, 1009–1014 (2008)PubMedCrossRef
69.
Zurück zum Zitat J.A. Leopold, A. Dam, B.A. Maron, A.W. Scribner, R. Liao, D.E. Handy, R.C. Stanton, B. Pitt, J. Loscalzo, Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat. Med. 13, 189–197 (2007)PubMedPubMedCentralCrossRef J.A. Leopold, A. Dam, B.A. Maron, A.W. Scribner, R. Liao, D.E. Handy, R.C. Stanton, B. Pitt, J. Loscalzo, Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat. Med. 13, 189–197 (2007)PubMedPubMedCentralCrossRef
70.
Zurück zum Zitat Y. Yuan, Y. Chen, P. Zhang, S. Huang, C. Zhu, G. Ding, B. Liu, T. Yang, A. Zhang, Mitochondrial dysfunction accounts for aldosterone-induced epithelial-to-mesenchymal transition of renal proximal tubular epithelial cells. Free Radic. Biol. Med. 53, 30–43 (2012)PubMedCrossRef Y. Yuan, Y. Chen, P. Zhang, S. Huang, C. Zhu, G. Ding, B. Liu, T. Yang, A. Zhang, Mitochondrial dysfunction accounts for aldosterone-induced epithelial-to-mesenchymal transition of renal proximal tubular epithelial cells. Free Radic. Biol. Med. 53, 30–43 (2012)PubMedCrossRef
71.
Zurück zum Zitat A. Zhang, Z. Jia, X. Guo, T. Yang, Aldosterone induces epithelial-mesenchymal transition via ROS of mitochondrial origin. Am. J. Physiol. Ren. Physiol. 293, F723–F731 (2007)CrossRef A. Zhang, Z. Jia, X. Guo, T. Yang, Aldosterone induces epithelial-mesenchymal transition via ROS of mitochondrial origin. Am. J. Physiol. Ren. Physiol. 293, F723–F731 (2007)CrossRef
72.
Zurück zum Zitat C. Zhu, S. Huang, Y. Yuan, G. Ding, R. Chen, B. Liu, T. Yang, A. Zhang, Mitochondrial dysfunction mediates aldosterone-induced podocyte damage: a therapeutic target of PPARgamma. Am. J. Pathol. 178, 2020–2031 (2011)PubMedPubMedCentralCrossRef C. Zhu, S. Huang, Y. Yuan, G. Ding, R. Chen, B. Liu, T. Yang, A. Zhang, Mitochondrial dysfunction mediates aldosterone-induced podocyte damage: a therapeutic target of PPARgamma. Am. J. Pathol. 178, 2020–2031 (2011)PubMedPubMedCentralCrossRef
73.
Zurück zum Zitat V.C. De Giusti, M.B. Nolly, A.M. Yeves, C.I. Caldiz, M.C. Villa-Abrille, G.E. Chiappe de Cingolani, I.L. Ennis, H.E. Cingolani, E.A. Aiello, Aldosterone stimulates the cardiac Na(+)/H(+) exchanger via transactivation of the epidermal growth factor receptor. Hypertension 58, 912–919 (2011)PubMedCrossRef V.C. De Giusti, M.B. Nolly, A.M. Yeves, C.I. Caldiz, M.C. Villa-Abrille, G.E. Chiappe de Cingolani, I.L. Ennis, H.E. Cingolani, E.A. Aiello, Aldosterone stimulates the cardiac Na(+)/H(+) exchanger via transactivation of the epidermal growth factor receptor. Hypertension 58, 912–919 (2011)PubMedCrossRef
74.
Zurück zum Zitat V.C. De Giusti, A. Orlowski, M.C. Ciancio, M.S. Espejo, L.A. Gonano, C.I. Caldiz, M.G. Vila Petroff, M.C. Villa-Abrille, E.A. Aiello, Aldosterone stimulates the cardiac sodium/bicarbonate cotransporter via activation of the g protein-coupled receptor gpr30. J. Mol. Cell. Cardiol. 89, 260–267 (2015)PubMedCrossRef V.C. De Giusti, A. Orlowski, M.C. Ciancio, M.S. Espejo, L.A. Gonano, C.I. Caldiz, M.G. Vila Petroff, M.C. Villa-Abrille, E.A. Aiello, Aldosterone stimulates the cardiac sodium/bicarbonate cotransporter via activation of the g protein-coupled receptor gpr30. J. Mol. Cell. Cardiol. 89, 260–267 (2015)PubMedCrossRef
75.
Zurück zum Zitat T.Y. Chun, L.J. Bloem, J.H. Pratt, Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. Endocrinology 144, 1712–1717 (2003)PubMedCrossRef T.Y. Chun, L.J. Bloem, J.H. Pratt, Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. Endocrinology 144, 1712–1717 (2003)PubMedCrossRef
76.
Zurück zum Zitat D. Nagata, M. Takahashi, K. Sawai, T. Tagami, T. Usui, A. Shimatsu, Y. Hirata, M. Naruse, Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension 48, 165–171 (2006)PubMedCrossRef D. Nagata, M. Takahashi, K. Sawai, T. Tagami, T. Usui, A. Shimatsu, Y. Hirata, M. Naruse, Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension 48, 165–171 (2006)PubMedCrossRef
77.
Zurück zum Zitat E.H. Bae, H.J. Cho, I.J. Kim, S.Y. Joo, J.H. Shin, S.K. Ma, J. Lee, S.W. Kim, Altered regulation of renal nitric oxide, atrial natriuretic peptide and cyclooxygenase systems in aldosterone escape in rats. Regul. Pept. 159, 117–122 (2010)PubMedCrossRef E.H. Bae, H.J. Cho, I.J. Kim, S.Y. Joo, J.H. Shin, S.K. Ma, J. Lee, S.W. Kim, Altered regulation of renal nitric oxide, atrial natriuretic peptide and cyclooxygenase systems in aldosterone escape in rats. Regul. Pept. 159, 117–122 (2010)PubMedCrossRef
78.
Zurück zum Zitat H.M. Thai, B.Q. Do, T.D. Tran, M.A. Gaballa, S. Goldman, Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production. J. Card. Fail. 12, 240–245 (2006)PubMedCrossRef H.M. Thai, B.Q. Do, T.D. Tran, M.A. Gaballa, S. Goldman, Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production. J. Card. Fail. 12, 240–245 (2006)PubMedCrossRef
79.
Zurück zum Zitat C.J. Hanke, T. O’Brien, K.A. Pritchard Jr., W.B. Campbell, Inhibition of adrenal cell aldosterone synthesis by endogenous nitric oxide release. Hypertension 35, 324–328 (2000)PubMedCrossRef C.J. Hanke, T. O’Brien, K.A. Pritchard Jr., W.B. Campbell, Inhibition of adrenal cell aldosterone synthesis by endogenous nitric oxide release. Hypertension 35, 324–328 (2000)PubMedCrossRef
80.
Zurück zum Zitat J.A. Muldowney 3rd, S.N. Davis, D.E. Vaughan, N.J. Brown, NO synthase inhibition increases aldosterone in humans. Hypertension 44, 739–745 (2004)PubMedCrossRef J.A. Muldowney 3rd, S.N. Davis, D.E. Vaughan, N.J. Brown, NO synthase inhibition increases aldosterone in humans. Hypertension 44, 739–745 (2004)PubMedCrossRef
81.
Zurück zum Zitat J.M. Sainz, C. Reche, M.A. Rabano, C. Mondillo, Z.J. Patrignani, J.M. Macarulla, O.P. Pignataro, M. Trueba, Effects of nitric oxide on aldosterone synthesis and nitric oxide synthase activity in glomerulosa cells from bovine adrenal gland. Endocrine 24, 61–71 (2004)PubMedCrossRef J.M. Sainz, C. Reche, M.A. Rabano, C. Mondillo, Z.J. Patrignani, J.M. Macarulla, O.P. Pignataro, M. Trueba, Effects of nitric oxide on aldosterone synthesis and nitric oxide synthase activity in glomerulosa cells from bovine adrenal gland. Endocrine 24, 61–71 (2004)PubMedCrossRef
82.
Zurück zum Zitat C.J. Hanke, W.B. Campbell, Endothelial cell nitric oxide inhibits aldosterone synthesis in zona glomerulosa cells: modulation by oxygen. Am. J. Physiol. Endocrinol. Metab. 279, E846–E854 (2000)PubMedCrossRef C.J. Hanke, W.B. Campbell, Endothelial cell nitric oxide inhibits aldosterone synthesis in zona glomerulosa cells: modulation by oxygen. Am. J. Physiol. Endocrinol. Metab. 279, E846–E854 (2000)PubMedCrossRef
83.
Zurück zum Zitat Le.T.Y. Loan, M. Mardini, V.M. Howell, J.W. Funder, A.W. Ashton, A.S. Mihailidou, Low-dose spironolactone prevents apoptosis repressor with caspase recruitment domain degradation during myocardial infarction. Hypertension 59, 1164–1169 (2012)CrossRef Le.T.Y. Loan, M. Mardini, V.M. Howell, J.W. Funder, A.W. Ashton, A.S. Mihailidou, Low-dose spironolactone prevents apoptosis repressor with caspase recruitment domain degradation during myocardial infarction. Hypertension 59, 1164–1169 (2012)CrossRef
84.
Zurück zum Zitat T.A. Williams, A. Verhovez, A. Milan, F. Veglio, P. Mulatero, Protective effect of spironolactone on endothelial cell apoptosis. Endocrinology 147, 2496–2505 (2006)PubMedCrossRef T.A. Williams, A. Verhovez, A. Milan, F. Veglio, P. Mulatero, Protective effect of spironolactone on endothelial cell apoptosis. Endocrinology 147, 2496–2505 (2006)PubMedCrossRef
85.
Zurück zum Zitat Y. Nakamura, S. Suzuki, T. Suzuki, K. Ono, I. Miura, F. Satoh, T. Moriya, H. Saito, S. Yamada, S. Ito, H. Sasano, MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling. Am. J. Pathol. 169, 362–371 (2006)PubMedPubMedCentralCrossRef Y. Nakamura, S. Suzuki, T. Suzuki, K. Ono, I. Miura, F. Satoh, T. Moriya, H. Saito, S. Yamada, S. Ito, H. Sasano, MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling. Am. J. Pathol. 169, 362–371 (2006)PubMedPubMedCentralCrossRef
86.
Zurück zum Zitat C. Crochemore, J. Lu, Y. Wu, Z. Liposits, N. Sousa, F. Holsboer, O.F. Almeida, Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation. Mol. Psychiatry 10, 790–798 (2005)PubMedCrossRef C. Crochemore, J. Lu, Y. Wu, Z. Liposits, N. Sousa, F. Holsboer, O.F. Almeida, Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation. Mol. Psychiatry 10, 790–798 (2005)PubMedCrossRef
87.
Zurück zum Zitat T. Nakamura, K. Kataoka, M. Fukuda, H. Nako, Y. Tokutomi, Y.F. Dong, H. Ichijo, H. Ogawa, S. Kim-Mitsuyama, Critical role of apoptosis signal-regulating kinase 1 in aldosterone/salt-induced cardiac inflammation and fibrosis. Hypertension 54, 544–551 (2009)PubMedCrossRef T. Nakamura, K. Kataoka, M. Fukuda, H. Nako, Y. Tokutomi, Y.F. Dong, H. Ichijo, H. Ogawa, S. Kim-Mitsuyama, Critical role of apoptosis signal-regulating kinase 1 in aldosterone/salt-induced cardiac inflammation and fibrosis. Hypertension 54, 544–551 (2009)PubMedCrossRef
88.
Zurück zum Zitat Y. Wei, A.T. Whaley-Connell, J. Habibi, J. Rehmer, N. Rehmer, K. Patel, M. Hayden, V. DeMarco, C.M. Ferrario, J.A. Ibdah, J.R. Sowers, Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation. Hypertension 53, 158–165 (2009)PubMedCrossRef Y. Wei, A.T. Whaley-Connell, J. Habibi, J. Rehmer, N. Rehmer, K. Patel, M. Hayden, V. DeMarco, C.M. Ferrario, J.A. Ibdah, J.R. Sowers, Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation. Hypertension 53, 158–165 (2009)PubMedCrossRef
89.
Zurück zum Zitat N. Queisser, N. Schupp, Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related cardiovascular and renal diseases. Free Radic. Biol. Med. 53, 314–327 (2012)PubMedCrossRef N. Queisser, N. Schupp, Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related cardiovascular and renal diseases. Free Radic. Biol. Med. 53, 314–327 (2012)PubMedCrossRef
90.
Zurück zum Zitat N. Queisser, N. Schupp, H. Stopper, R. Schinzel, P.I. Oteiza, Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase. Free Radic. Biol. Med. 51, 1996–2006 (2011)PubMedCrossRef N. Queisser, N. Schupp, H. Stopper, R. Schinzel, P.I. Oteiza, Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase. Free Radic. Biol. Med. 51, 1996–2006 (2011)PubMedCrossRef
91.
Zurück zum Zitat V. Leroy, S. De Seigneux, V. Agassiz, U. Hasler, M.E. Rafestin-Oblin, M. Vinciguerra, P.Y. Martin, E. Feraille, Aldosterone activates NF-kappaB in the collecting duct. J. Am. Soc. Nephrol. 20, 131–144 (2009)PubMedPubMedCentralCrossRef V. Leroy, S. De Seigneux, V. Agassiz, U. Hasler, M.E. Rafestin-Oblin, M. Vinciguerra, P.Y. Martin, E. Feraille, Aldosterone activates NF-kappaB in the collecting duct. J. Am. Soc. Nephrol. 20, 131–144 (2009)PubMedPubMedCentralCrossRef
92.
Zurück zum Zitat S.U. Sonder, A. Woetmann, N. Odum, K. Bendtzen, Spironolactone induces apoptosis and inhibits NF-kappaB independent of the mineralocorticoid receptor. Apoptosis 11, 2159–2165 (2006)PubMedCrossRef S.U. Sonder, A. Woetmann, N. Odum, K. Bendtzen, Spironolactone induces apoptosis and inhibits NF-kappaB independent of the mineralocorticoid receptor. Apoptosis 11, 2159–2165 (2006)PubMedCrossRef
93.
Zurück zum Zitat J.C. Reil, M. Hohl, S. Selejan, P. Lipp, F. Drautz, A. Kazakow, B.M. Munz, P. Muller, P. Steendijk, G.H. Reil, M.A. Allessie, M. Bohm, H.R. Neuberger, Aldosterone promotes atrial fibrillation. Eur. Heart J. 33, 2098–2108 (2012)PubMedCrossRef J.C. Reil, M. Hohl, S. Selejan, P. Lipp, F. Drautz, A. Kazakow, B.M. Munz, P. Muller, P. Steendijk, G.H. Reil, M.A. Allessie, M. Bohm, H.R. Neuberger, Aldosterone promotes atrial fibrillation. Eur. Heart J. 33, 2098–2108 (2012)PubMedCrossRef
94.
Zurück zum Zitat G.M. Kuster, E. Kotlyar, M.K. Rude, D.A. Siwik, R. Liao, W.S. Colucci, F. Sam, Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 111, 420–427 (2005)PubMedCrossRef G.M. Kuster, E. Kotlyar, M.K. Rude, D.A. Siwik, R. Liao, W.S. Colucci, F. Sam, Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 111, 420–427 (2005)PubMedCrossRef
95.
Zurück zum Zitat A. Di Zhang, A. Nguyen Dinh Cat, C. Soukaseum, B. Escoubet, A. Cherfa, S. Messaoudi, C. Delcayre, J.L. Samuel, F. Jaisser, Cross-talk between mineralocorticoid and angiotensin II signaling for cardiac remodeling. Hypertension 52, 1060–1067 (2008)PubMedCrossRef A. Di Zhang, A. Nguyen Dinh Cat, C. Soukaseum, B. Escoubet, A. Cherfa, S. Messaoudi, C. Delcayre, J.L. Samuel, F. Jaisser, Cross-talk between mineralocorticoid and angiotensin II signaling for cardiac remodeling. Hypertension 52, 1060–1067 (2008)PubMedCrossRef
96.
Zurück zum Zitat G. Suzuki, H. Morita, T. Mishima, V.G. Sharov, A. Todor, E.J. Tanhehco, A.E. Rudolph, E.G. McMahon, S. Goldstein, H.N. Sabbah, Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation 106, 2967–2972 (2002)PubMedCrossRef G. Suzuki, H. Morita, T. Mishima, V.G. Sharov, A. Todor, E.J. Tanhehco, A.E. Rudolph, E.G. McMahon, S. Goldstein, H.N. Sabbah, Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation 106, 2967–2972 (2002)PubMedCrossRef
97.
Zurück zum Zitat M.R. Ward, P. Kanellakis, D. Ramsey, J. Funder, A. Bobik, Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries. Circulation 104, 467–472 (2001)PubMedCrossRef M.R. Ward, P. Kanellakis, D. Ramsey, J. Funder, A. Bobik, Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries. Circulation 104, 467–472 (2001)PubMedCrossRef
98.
Zurück zum Zitat J. Qu, F.M. Volpicelli, L.I. Garcia, N. Sandeep, J. Zhang, L. Marquez-Rosado, P.D. Lampe, G.I. Fishman, Gap junction remodeling and spironolactone-dependent reverse remodeling in the hypertrophied heart. Circ. Res. 104, 365–371 (2009)PubMedCrossRef J. Qu, F.M. Volpicelli, L.I. Garcia, N. Sandeep, J. Zhang, L. Marquez-Rosado, P.D. Lampe, G.I. Fishman, Gap junction remodeling and spironolactone-dependent reverse remodeling in the hypertrophied heart. Circ. Res. 104, 365–371 (2009)PubMedCrossRef
99.
Zurück zum Zitat P. Mulder, V. Mellin, J. Favre, M. Vercauteren, I. Remy-Jouet, C. Monteil, V. Richard, S. Renet, J.P. Henry, A.Y. Jeng, R.L. Webb, C. Thuillez, Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone. Eur. Heart J. 29, 2171–2179 (2008)PubMedCrossRef P. Mulder, V. Mellin, J. Favre, M. Vercauteren, I. Remy-Jouet, C. Monteil, V. Richard, S. Renet, J.P. Henry, A.Y. Jeng, R.L. Webb, C. Thuillez, Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone. Eur. Heart J. 29, 2171–2179 (2008)PubMedCrossRef
100.
Zurück zum Zitat G.P. Vyssoulis, E.A. Karpanou, V.E. Tzamou, S.M. Kyvelou, A.P. Michaelidis, T.P. Gialernios, D.V. Cokkinos, C.I. Stefanadis, Aldosterone levels and stroke incidence in essential hypertensive patients. Int. J. Cardiol. 144, 171–172 (2010)PubMedCrossRef G.P. Vyssoulis, E.A. Karpanou, V.E. Tzamou, S.M. Kyvelou, A.P. Michaelidis, T.P. Gialernios, D.V. Cokkinos, C.I. Stefanadis, Aldosterone levels and stroke incidence in essential hypertensive patients. Int. J. Cardiol. 144, 171–172 (2010)PubMedCrossRef
101.
Zurück zum Zitat B.S. Huang, F.H. Leenen, The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction. Curr. Heart Fail. Rep. 6, 81–88 (2009)PubMedCrossRef B.S. Huang, F.H. Leenen, The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction. Curr. Heart Fail. Rep. 6, 81–88 (2009)PubMedCrossRef
102.
Zurück zum Zitat M. Joels, H. Karst, R. DeRijk, E.R. de Kloet, The coming out of the brain mineralocorticoid receptor. Trends Neurosci. 31, 1–7 (2008)PubMedCrossRef M. Joels, H. Karst, R. DeRijk, E.R. de Kloet, The coming out of the brain mineralocorticoid receptor. Trends Neurosci. 31, 1–7 (2008)PubMedCrossRef
103.
Zurück zum Zitat E.A. Young, J.F. Lopez, V. Murphy-Weinberg, S.J. Watson, H. Akil, Mineralocorticoid receptor function in major depression. Arch. Gen. Psychiatry 60, 24–28 (2003)PubMedCrossRef E.A. Young, J.F. Lopez, V. Murphy-Weinberg, S.J. Watson, H. Akil, Mineralocorticoid receptor function in major depression. Arch. Gen. Psychiatry 60, 24–28 (2003)PubMedCrossRef
104.
Zurück zum Zitat C. Otte, K. Wingenfeld, L.K. Kuehl, S. Richter, F. Regen, D. Piber, K. Hinkelmann, Cognitive function in older adults with major depression: Effects of mineralocorticoid receptor stimulation. J. Psychiatr. Res. 69, 120–125 (2015)PubMedCrossRef C. Otte, K. Wingenfeld, L.K. Kuehl, S. Richter, F. Regen, D. Piber, K. Hinkelmann, Cognitive function in older adults with major depression: Effects of mineralocorticoid receptor stimulation. J. Psychiatr. Res. 69, 120–125 (2015)PubMedCrossRef
105.
Zurück zum Zitat V.S. Chhokar, Y. Sun, S.K. Bhattacharya, R.A. Ahokas, L.K. Myers, Z. Xing, R.A. Smith, I.C. Gerling, K.T. Weber, Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 111, 871–878 (2005)PubMedCrossRef V.S. Chhokar, Y. Sun, S.K. Bhattacharya, R.A. Ahokas, L.K. Myers, Z. Xing, R.A. Smith, I.C. Gerling, K.T. Weber, Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 111, 871–878 (2005)PubMedCrossRef
106.
Zurück zum Zitat Y. Mizuno, M. Yoshimura, H. Yasue, T. Sakamoto, H. Ogawa, K. Kugiyama, E. Harada, M. Nakayama, S. Nakamura, T. Ito, Y. Shimasaki, Y. Saito, K. Nakao, Aldosterone production is activated in failing ventricle in humans. Circulation 103, 72–77 (2001)PubMedCrossRef Y. Mizuno, M. Yoshimura, H. Yasue, T. Sakamoto, H. Ogawa, K. Kugiyama, E. Harada, M. Nakayama, S. Nakamura, T. Ito, Y. Shimasaki, Y. Saito, K. Nakao, Aldosterone production is activated in failing ventricle in humans. Circulation 103, 72–77 (2001)PubMedCrossRef
107.
Zurück zum Zitat G. Guder, J. Bauersachs, S. Frantz, D. Weismann, B. Allolio, G. Ertl, C.E. Angermann, S. Stork, Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation 115, 1754–1761 (2007)PubMedCrossRef G. Guder, J. Bauersachs, S. Frantz, D. Weismann, B. Allolio, G. Ertl, C.E. Angermann, S. Stork, Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation 115, 1754–1761 (2007)PubMedCrossRef
108.
Zurück zum Zitat F.M. Gutierrez-Marcos, A. Fernandez-Cruz, J. Gutkowska, C. Herrero, A. Blesa, V. Estrada, C. Loscos, J.M. Lopez-Novoa, Atrial natriuretic peptide in patients with acute myocardial infarction without functional heart failure. Eur. Heart J. 12, 503–507 (1991)PubMedCrossRef F.M. Gutierrez-Marcos, A. Fernandez-Cruz, J. Gutkowska, C. Herrero, A. Blesa, V. Estrada, C. Loscos, J.M. Lopez-Novoa, Atrial natriuretic peptide in patients with acute myocardial infarction without functional heart failure. Eur. Heart J. 12, 503–507 (1991)PubMedCrossRef
109.
Zurück zum Zitat F. Beygui, J.P. Collet, J.J. Benoliel, N. Vignolles, R. Dumaine, O. Barthelemy, G. Montalescot, High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation 114, 2604–2610 (2006)PubMedCrossRef F. Beygui, J.P. Collet, J.J. Benoliel, N. Vignolles, R. Dumaine, O. Barthelemy, G. Montalescot, High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation 114, 2604–2610 (2006)PubMedCrossRef
110.
Zurück zum Zitat B. Pitt, W. Remme, F. Zannad, J. Neaton, F. Martinez, B. Roniker, R. Bittman, S. Hurley, J. Kleiman, M. Gatlin, Eplerenone Post-Acute Myocardial Infarction Heart Failure E, Survival Study I, Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 348, 1309–1321 (2003).PubMedCrossRef B. Pitt, W. Remme, F. Zannad, J. Neaton, F. Martinez, B. Roniker, R. Bittman, S. Hurley, J. Kleiman, M. Gatlin, Eplerenone Post-Acute Myocardial Infarction Heart Failure E, Survival Study I, Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 348, 1309–1321 (2003).PubMedCrossRef
111.
Zurück zum Zitat B. Pitt, F. Zannad, W.J. Remme, R. Cody, A. Castaigne, A. Perez, J. Palensky, J. Wittes, The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 341, 709–717 (1999)PubMedCrossRef B. Pitt, F. Zannad, W.J. Remme, R. Cody, A. Castaigne, A. Perez, J. Palensky, J. Wittes, The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl. J. Med. 341, 709–717 (1999)PubMedCrossRef
112.
Zurück zum Zitat M.B. Nolly, C.I. Caldiz, A.M. Yeves, M.C. Villa-Abrille, P.E. Morgan, N. Amado Mondaca, E.L. Portiansky, G.E. Chiappe de Cingolani, H.E. Cingolani, I.L. Ennis, The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium. J. Mol. Cell. Cardiol. 67, 60–68 (2014)PubMedCrossRef M.B. Nolly, C.I. Caldiz, A.M. Yeves, M.C. Villa-Abrille, P.E. Morgan, N. Amado Mondaca, E.L. Portiansky, G.E. Chiappe de Cingolani, H.E. Cingolani, I.L. Ennis, The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium. J. Mol. Cell. Cardiol. 67, 60–68 (2014)PubMedCrossRef
113.
Zurück zum Zitat B.R. Palmer, A.P. Pilbrow, C.M. Frampton, T.G. Yandle, L. Skelton, M.G. Nicholls, A.M. Richards, Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction. Eur. Heart J. 29, 2489–2496 (2008)PubMedCrossRef B.R. Palmer, A.P. Pilbrow, C.M. Frampton, T.G. Yandle, L. Skelton, M.G. Nicholls, A.M. Richards, Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction. Eur. Heart J. 29, 2489–2496 (2008)PubMedCrossRef
114.
Zurück zum Zitat M. Quinkler, D. Zehnder, K.S. Eardley, J. Lepenies, A.J. Howie, S.V. Hughes, P. Cockwell, M. Hewison, P.M. Stewart, Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation 112, 1435–1443 (2005)PubMedCrossRef M. Quinkler, D. Zehnder, K.S. Eardley, J. Lepenies, A.J. Howie, S.V. Hughes, P. Cockwell, M. Hewison, P.M. Stewart, Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation 112, 1435–1443 (2005)PubMedCrossRef
115.
Zurück zum Zitat J.P. Bertocchio, D.G. Warnock, F. Jaisser, Mineralocorticoid receptor activation and blockade: an emerging paradigm in chronic kidney disease. Kidney Int. 79, 1051–1060 (2011)PubMedCrossRef J.P. Bertocchio, D.G. Warnock, F. Jaisser, Mineralocorticoid receptor activation and blockade: an emerging paradigm in chronic kidney disease. Kidney Int. 79, 1051–1060 (2011)PubMedCrossRef
116.
Zurück zum Zitat K. Ando, H. Ohtsu, S. Uchida, S. Kaname, Y. Arakawa, T. Fujita, E.S. Group, Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2, 944–953 (2014)PubMedCrossRef K. Ando, H. Ohtsu, S. Uchida, S. Kaname, Y. Arakawa, T. Fujita, E.S. Group, Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2, 944–953 (2014)PubMedCrossRef
117.
Zurück zum Zitat G.L. Bakris, R. Agarwal, J.C. Chan, M.E. Cooper, R.T. Gansevoort, H. Haller, G. Remuzzi, P. Rossing, R.E. Schmieder, C. Nowack, P. Kolkhof, A. Joseph, A. Pieper, N. Kimmeskamp-Kirschbaum, L.M. Ruilope; Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy Study G., Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 314, 884–894 (2015)PubMedCrossRef G.L. Bakris, R. Agarwal, J.C. Chan, M.E. Cooper, R.T. Gansevoort, H. Haller, G. Remuzzi, P. Rossing, R.E. Schmieder, C. Nowack, P. Kolkhof, A. Joseph, A. Pieper, N. Kimmeskamp-Kirschbaum, L.M. Ruilope; Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy Study G., Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 314, 884–894 (2015)PubMedCrossRef
118.
Zurück zum Zitat T. Kosugi, M. Heinig, T. Nakayama, S. Matsuo, T. Nakagawa, eNOS knockout mice with advanced diabetic nephropathy have less benefit from renin-angiotensin blockade than from aldosterone receptor antagonists. Am. J. Pathol. 176, 619–629 (2010)PubMedPubMedCentralCrossRef T. Kosugi, M. Heinig, T. Nakayama, S. Matsuo, T. Nakagawa, eNOS knockout mice with advanced diabetic nephropathy have less benefit from renin-angiotensin blockade than from aldosterone receptor antagonists. Am. J. Pathol. 176, 619–629 (2010)PubMedPubMedCentralCrossRef
119.
Zurück zum Zitat T. Suehiro, K. Tsuruya, H. Ikeda, J. Toyonaga, S. Yamada, H. Noguchi, M. Tokumoto, T. Kitazono, Systemic aldosterone, but not angiotensin II, plays a pivotal role in the pathogenesis of renal injury in chronic nitric oxide-deficient male rats. Endocrinology 156, 2657–2666 (2015).PubMedCrossRef T. Suehiro, K. Tsuruya, H. Ikeda, J. Toyonaga, S. Yamada, H. Noguchi, M. Tokumoto, T. Kitazono, Systemic aldosterone, but not angiotensin II, plays a pivotal role in the pathogenesis of renal injury in chronic nitric oxide-deficient male rats. Endocrinology 156, 2657–2666 (2015).PubMedCrossRef
120.
Zurück zum Zitat B. Musicki, A.J. Bella, T.J. Bivalacqua, K.P. Davies, M.E. DiSanto, N.F. Gonzalez-Cadavid, J.L. Hannan, N.N. Kim, C.A. Podlasek, C.J. Wingard, A.L. Burnett, Basic science evidence for the link between erectile dysfunction and cardiometabolic dysfunction. J. Sex. Med. 12, 2233–2255 (2015)PubMedPubMedCentralCrossRef B. Musicki, A.J. Bella, T.J. Bivalacqua, K.P. Davies, M.E. DiSanto, N.F. Gonzalez-Cadavid, J.L. Hannan, N.N. Kim, C.A. Podlasek, C.J. Wingard, A.L. Burnett, Basic science evidence for the link between erectile dysfunction and cardiometabolic dysfunction. J. Sex. Med. 12, 2233–2255 (2015)PubMedPubMedCentralCrossRef
121.
Zurück zum Zitat J.T. Clark, A. Sahu, J.J. Mrotek, S.P. Kalra, Sexual function and neuropeptide Y levels in selected brain regions in male spontaneously hypertensive rats. Am. J. Physiol. 261, R1234–R1241 (1991)PubMed J.T. Clark, A. Sahu, J.J. Mrotek, S.P. Kalra, Sexual function and neuropeptide Y levels in selected brain regions in male spontaneously hypertensive rats. Am. J. Physiol. 261, R1234–R1241 (1991)PubMed
122.
Zurück zum Zitat F. Wu, S. Mao, T. Yu, H. Jiang, Q. Ding, G. Xu, Elevated plasma aldosterone is an independent risk factor for erectile dysfunction in men. World J. Urol. 34, 999–1007 (2016)PubMedCrossRef F. Wu, S. Mao, T. Yu, H. Jiang, Q. Ding, G. Xu, Elevated plasma aldosterone is an independent risk factor for erectile dysfunction in men. World J. Urol. 34, 999–1007 (2016)PubMedCrossRef
123.
Zurück zum Zitat F.A. DeLano, G.W. Schmid-Schonbein, Enhancement of glucocorticoid and mineralocorticoid receptor density in the microcirculation of the spontaneously hypertensive rat. Microcirculation 11, 69–78 (2004)PubMedCrossRef F.A. DeLano, G.W. Schmid-Schonbein, Enhancement of glucocorticoid and mineralocorticoid receptor density in the microcirculation of the spontaneously hypertensive rat. Microcirculation 11, 69–78 (2004)PubMedCrossRef
124.
Zurück zum Zitat M. Zhao, I. Celerier, E. Bousquet, J.C. Jeanny, L. Jonet, M. Savoldelli, O. Offret, A. Curan, N. Farman, F. Jaisser, F. Behar-Cohen, Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. J. Clin. Invest. 122, 2672–2679 (2012)PubMedPubMedCentralCrossRef M. Zhao, I. Celerier, E. Bousquet, J.C. Jeanny, L. Jonet, M. Savoldelli, O. Offret, A. Curan, N. Farman, F. Jaisser, F. Behar-Cohen, Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. J. Clin. Invest. 122, 2672–2679 (2012)PubMedPubMedCentralCrossRef
125.
Zurück zum Zitat M. Lainscak, F. Pelliccia, G. Rosano, C. Vitale, M. Schiariti, C. Greco, G. Speziale, C. Gaudio, Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone. Int. J. Cardiol. 200, 25–29 (2015)PubMedCrossRef M. Lainscak, F. Pelliccia, G. Rosano, C. Vitale, M. Schiariti, C. Greco, G. Speziale, C. Gaudio, Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone. Int. J. Cardiol. 200, 25–29 (2015)PubMedCrossRef
126.
Zurück zum Zitat H.S. Zarren, P.M. Black, Unilateral gynecomastia and impotence during low-dose spironolactone administration in men. Mil. Med. 140, 417–419 (1975)PubMedCrossRef H.S. Zarren, P.M. Black, Unilateral gynecomastia and impotence during low-dose spironolactone administration in men. Mil. Med. 140, 417–419 (1975)PubMedCrossRef
127.
Zurück zum Zitat D.J. Greenblatt, J. Koch-Weser, Gynecomastia and impotence: complications of spironolactone therapy. JAMA 223, 82 (1973)PubMedCrossRef D.J. Greenblatt, J. Koch-Weser, Gynecomastia and impotence: complications of spironolactone therapy. JAMA 223, 82 (1973)PubMedCrossRef
128.
Zurück zum Zitat M. Epstein, D.A. Calhoun, Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J. Clin. Hypertens. 13, 644–648 (2011)CrossRef M. Epstein, D.A. Calhoun, Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J. Clin. Hypertens. 13, 644–648 (2011)CrossRef
129.
Zurück zum Zitat C. Bonne, J.P. Raynaud, Mode of spironolactone anti-androgenic action: inhibition of androstanolone binding to rat prostate androgen receptor. Mol. Cell. Endocrinol. 2, 59–67 (1974)PubMedCrossRef C. Bonne, J.P. Raynaud, Mode of spironolactone anti-androgenic action: inhibition of androstanolone binding to rat prostate androgen receptor. Mol. Cell. Endocrinol. 2, 59–67 (1974)PubMedCrossRef
130.
Zurück zum Zitat F. Zannad, J.J. McMurray, H. Krum, D.J. van Veldhuisen, K. Swedberg, H. Shi, J. Vincent, S.J. Pocock, B. Pitt, E.-H.S. Group, Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 364, 11–21 (2011)PubMedCrossRef F. Zannad, J.J. McMurray, H. Krum, D.J. van Veldhuisen, K. Swedberg, H. Shi, J. Vincent, S.J. Pocock, B. Pitt, E.-H.S. Group, Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 364, 11–21 (2011)PubMedCrossRef
131.
Zurück zum Zitat B. Pitt, L. Kober, P. Ponikowski, M. Gheorghiade, G. Filippatos, H. Krum, C. Nowack, P. Kolkhof, S.Y. Kim, F. Zannad, Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur. Heart J. 34, 2453–2463 (2013)PubMedPubMedCentralCrossRef B. Pitt, L. Kober, P. Ponikowski, M. Gheorghiade, G. Filippatos, H. Krum, C. Nowack, P. Kolkhof, S.Y. Kim, F. Zannad, Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur. Heart J. 34, 2453–2463 (2013)PubMedPubMedCentralCrossRef
132.
Zurück zum Zitat M. Hargovan, A. Ferro, Aldosterone synthase inhibitors in hypertension: current status and future possibilities. JRSM Cardiovasc. Dis. 3, 2048004014522440 (2014)PubMedPubMedCentral M. Hargovan, A. Ferro, Aldosterone synthase inhibitors in hypertension: current status and future possibilities. JRSM Cardiovasc. Dis. 3, 2048004014522440 (2014)PubMedPubMedCentral
133.
Zurück zum Zitat A. Fiebeler, J. Nussberger, E. Shagdarsuren, S. Rong, G. Hilfenhaus, N. Al-Saadi, R. Dechend, M. Wellner, S. Meiners, C. Maser-Gluth, A.Y. Jeng, R.L. Webb, F.C. Luft, D.N. Muller, Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation 111, 3087–3094 (2005)PubMedCrossRef A. Fiebeler, J. Nussberger, E. Shagdarsuren, S. Rong, G. Hilfenhaus, N. Al-Saadi, R. Dechend, M. Wellner, S. Meiners, C. Maser-Gluth, A.Y. Jeng, R.L. Webb, F.C. Luft, D.N. Muller, Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation 111, 3087–3094 (2005)PubMedCrossRef
134.
Zurück zum Zitat X. Bertagna, R. Pivonello, M. Fleseriu, Y. Zhang, P. Robinson, A. Taylor, C.E. Watson, M. Maldonado, A.H. Hamrahian, M. Boscaro, B.M. Biller, LCI699, a potent 11beta-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J. Clin. Endocrinol. Metab. 99, 1375–1383 (2014)PubMedCrossRef X. Bertagna, R. Pivonello, M. Fleseriu, Y. Zhang, P. Robinson, A. Taylor, C.E. Watson, M. Maldonado, A.H. Hamrahian, M. Boscaro, B.M. Biller, LCI699, a potent 11beta-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J. Clin. Endocrinol. Metab. 99, 1375–1383 (2014)PubMedCrossRef
135.
Zurück zum Zitat A. Granata, G. Tirabassi, V. Pugni, G. Arnaldi, M. Boscaro, C. Carani, G. Balercia, Sexual dysfunctions in men affected by autoimmune Addison’s disease before and after short-term gluco- and mineralocorticoid replacement therapy. J. Sex. Med. 10, 2036–2043 (2013)PubMedCrossRef A. Granata, G. Tirabassi, V. Pugni, G. Arnaldi, M. Boscaro, C. Carani, G. Balercia, Sexual dysfunctions in men affected by autoimmune Addison’s disease before and after short-term gluco- and mineralocorticoid replacement therapy. J. Sex. Med. 10, 2036–2043 (2013)PubMedCrossRef
Metadaten
Titel
The emerging role of aldosterone/mineralocorticoid receptors in the pathogenesis of erectile dysfunction
verfasst von
Fei Wu
Yun Lin
Qingyong Liu
Publikationsdatum
02.05.2018
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-018-1610-8

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