Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Vasopressin: a novel target for the prevention and retardation of kidney disease?

Abstract

After several decades during which little attention was paid to vasopressin and/or urine concentration in clinical practice, interest in vasopressin has renewed with the availability of new, potent, orally active vasopressin-receptor antagonists—the vaptans—and with the results of epidemiological studies evaluating copeptin (a surrogate marker of vasopressin) in large population-based cohorts. Several experimental studies in rats and mice had previously shown that vasopressin, acting via vasopressin V2 antidiuretic receptors, contributes to the progression of chronic kidney disease; in particular, to autosomal dominant polycystic kidney disease. New epidemiological studies now suggest a role for vasopressin in the pathogenesis of diabetes mellitus and metabolic disorders via activation of hepatic V1a and/or pancreatic islet V1b receptors. The first part of this Review describes the adverse effects of vasopressin, as revealed by clinical and experimental studies in kidney diseases, hypertension, diabetes and the metabolic syndrome. The second part provides insights into vasopressin physiology and pathophysiology that may be relevant to the understanding of these adverse effects and that are linked to the excretion of concentrated nitrogen wastes and associated hyperfiltration. Collectively, the studies reviewed here suggest that more attention should be given to the vasopressin–thirst–urine concentration axis in clinical investigations and in patient care. Whether selective blockade of the different vasopressin receptors may provide therapeutic benefits beyond their present indication in hyponatraemia requires new clinical trials.

Key Points

  • Vasopressin is a hormone that is involved in water conservation, a function of marked importance for immediate survival; however, its long-term adverse effects have only recently begun to be appreciated

  • Vasopressin, acting via renal V2 receptors, might indirectly reduce the efficiency of sodium and urea excretion, and increase glomerular filtration rate, imposing an increased energetic demand on the kidney

  • In the long term, these vasopressin-induced changes might contribute to the progression of chronic kidney disease, diabetic nephropathy, and salt-sensitive hypertension

  • Vasopressin participates in cyst growth in autosomal dominant polycystic kidney disease; in a prospective 3-year double-blind placebo-controlled trial, the V2-receptor antagonist tolvaptan significantly slowed progression of this disease

  • Some studies suggest that vasopressin might participate in the regulation of glucose and lipid metabolism through actions on hepatic V1a and pancreatic islet V1b receptors

  • Various cohort studies have revealed associations between high copeptin level or low water intake and the prevalence or incidence of hyperglycaemia, type 2 diabetes and the metabolic syndrome

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Relationship between annual decline in eGFR or albuminuria and vasopressin-related indices in population-based cohorts.
Figure 2: The association between urine concentration and chronic kidney disease progression or albuminuria in rats.
Figure 3: Relationship between GFR, urinary flow rate, osmolality, relative urea concentration and fractional excretion of urea.
Figure 4: The 'J-shaped' relationship between GFR and urine osmolality.
Figure 5: The similar causes and consequences of high protein intake and high urinary concentrating activity on the kidney.

Similar content being viewed by others

References

  1. Addis, T. Glomerular nephritis (The Macmillan Company, New York, 1949).

    Google Scholar 

  2. Serradeil-Le Gal, C. et al. Nonpeptide vasopressin receptor antagonists: development of selective and orally active V1a, V2 and V1b receptor ligands. Prog. Brain Res. 139, 197–210 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Miyazaki, T., Fujiki, H., Yamamura, Y., Nakamura, S. & Mori, T. Tolvaptan, an orally active vasopressin V(2)-receptor antagonist—pharmacology and clinical trials. Cardiovasc. Drug Rev. 25, 1–13 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Greenberg, A. & Verbalis, J. G. Vasopressin receptor antagonists. Kidney Int. 69, 2124–2130 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Torres, V. E. Role of vasopressin antagonists. Clin. J. Am. Soc. Nephrol. 3, 1212–1218 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Decaux, G., Soupart, A. & Vassart, G. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet 371, 1624–1632 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Morgenthaler, N. G., Struck, J., Alonso, C. & Bergmann, A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin. Chem. 52, 112–119 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Morgenthaler, N. G. Copeptin: a biomarker of cardiovascular and renal function. Congest. Heart Fail. 16 (Suppl. 1), S37–S44 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Morel, A., O'Carroll, A. M., Brownstein, M. J. & Lolait, S. J. Molecular cloning and expression of a rat V1a arginine vasopressin receptor. Nature 356, 523–526 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Birnbaumer, M. et al. Molecular cloning of the receptor for human antidiuretic hormone. Nature 357, 333–335 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Zingg, H. H. Vasopressin and oxytocin receptors. Baillieres Clin. Endocrinol. Metab. 10, 75–96 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Bichet, D. G. Vasopressin receptors in health and disease. Kidney Int. 49, 1706–1711 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Boertien, W. E. et al. Copeptin, a surrogate marker for vasopressin, is associated with kidney function decline in subjects with autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 27, 4131–4137 (2012).

    Article  CAS  PubMed  Google Scholar 

  14. Clark, W. F. et al. Urine volume and change in estimated GFR in a community-based cohort study. Clin. J. Am. Soc. Nephrol. 6, 2634–2641 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Meijer, E. et al. Copeptin, a surrogate marker of vasopressin, is associated with accelerated renal function decline in renal transplant recipients. Transplantation 88, 561–567 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Meijer, E. et al. Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 361–368 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Meijer, E. et al. Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int. 77, 29–36 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Strippoli, G. F. et al. Fluid and nutrient intake and risk of chronic kidney disease. Nephrology (Carlton) 16, 326–334 (2011).

    Article  Google Scholar 

  19. Torres, V. E. et al. Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 640–647 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Plischke, M., Kohl, M., Handisurya, A. & Haas, M. Association between urine osmolality and progression of chronic renal failure: A cohort study [abstract TH-PO322]. J. Am. Soc. Nephrol. 23, 169A (2012).

    Google Scholar 

  21. Boertien, W. E. et al. Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort. Am. J. Kidney Dis. http://dx.doi.org/10.1053/j.ajkd.2012.08.038.

  22. Higashihara, E. et al. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clin. J. Am. Soc. Nephrol. 6, 2499–2507 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pan, A. et al. Plain-water intake and risk of type 2 diabetes in young and middle-aged women. Am. J. Clin. Nutr. 95, 1454–1460 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Roussel, R. et al. Low water intake and risk for new-onset hyperglycemia. Diabetes Care 34, 2551–2554 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Torres, V. E. et al. Rationale and design of the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes) 3–4 Study. Am. J. Kidney Dis. 57, 692–699 (2011).

    Article  CAS  PubMed  Google Scholar 

  26. Abbasi, A. et al. Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Diabetologia 55, 1963–1970 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. Enhörning, S. et al. Copeptin, a marker of vasopressin, in abdominal obesity, diabetes and microalbuminuria: the prospective Malmo Diet and Cancer Study cardiovascular cohort. Int. J. Obes. (Lond.) http://dx.doi.org/10.1038/ijo.2012.88.

  28. Enhörning, S. et al. Relation between human vasopressin 1a gene variance, fat intake, and diabetes. Am. J. Clin. Nutr. 89, 400–406 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Enhörning, S. et al. Plasma copeptin and the risk of diabetes mellitus. Circulation 121, 2102–2108 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Torres, V. E. et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 367, 2407–2418 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Valtin, H. “Drink at least eight glasses of water a day.” Really? Is there scientific evidence for “8 × 8”? Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R993–R1004 (2002).

    Article  PubMed  Google Scholar 

  32. Wenzel, U. O., Hebert, L. A., Stahl, R. A. & Krenz, I. My doctor said I should drink a lot! Recommendations for fluid intake in patients with chronic kidney disease. Clin. J. Am. Soc. Nephrol. 1, 344–346 (2006).

    Article  PubMed  Google Scholar 

  33. McCartney, M. Waterlogged? BMJ 343, d4280 (2011).

    Article  PubMed  Google Scholar 

  34. Negoianu, D. & Goldfarb, S. Just add water. J. Am. Soc. Nephrol. 19, 1041–1043 (2008).

    Article  PubMed  Google Scholar 

  35. Hebert, L. A., Greene, T., Levey, A., Falkenhain, M. E. & Klahr, S. High urine volume and low urine osmolality are risk factors for faster progression of renal disease. Am. J. Kidney Dis. 41, 962–971 (2003).

    Article  PubMed  Google Scholar 

  36. Bouby, N., Bachmann, S., Bichet, D. & Bankir, L. Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. Am. J. Physiol. 258, F973–F979 (1990).

    CAS  PubMed  Google Scholar 

  37. Sugiura, T. et al. High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: possible role of TGF-beta. Kidney Int. 55, 1800–1810 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Bouby, N., Hassler, C. & Bankir, L. Contribution of vasopressin to progression of chronic renal failure: study in Brattleboro rats. Life Sci. 65, 991–1004 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Bregman, R., Boim, M. A., Santos, O. F., Ramos, O. L. & Schor, N. Effects of systemic hypertension, antidiuretic hormone, and prostaglandins on remnant nephrons. Hypertension 15, 172–175 (1990).

    Article  Google Scholar 

  40. Okada, H., Suzuki, H., Kanno, Y. & Saruta, T. Evidence for the involvement of vasopressin in the pathophysiology of adriamycin-induced nephropathy in rats. Nephron 72, 667–672 (1996).

    Article  CAS  PubMed  Google Scholar 

  41. Perico, N. et al. V1/V2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. Kidney Int. 76, 960–967 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Bardoux, P. et al. Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system. Nephrol. Dial. Transplant. 18, 497–506 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Bardoux, P. et al. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. Proc. Natl Acad. Sci. USA 96, 10397–10402 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fernandes, S. et al. Chronic V2 vasopressin receptor stimulation increases basal blood pressure and exacerbates deoxycorticosterone acetate-salt hypertension. Endocrinology 143, 2759–2766 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Bardoux, P., Bruneval, P., Heudes, D., Bouby, N. & Bankir, L. Diabetes-induced albuminuria: role of antidiuretic hormone as revealed by chronic V2 receptor antagonism in rats. Nephrol. Dial. Transplant. 18, 1755–1763 (2003).

    Article  CAS  PubMed  Google Scholar 

  46. Windt, W. A. et al. Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy. J. Renin Angiotensin Aldosterone Syst. 7, 217–224 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Okada, T. et al. Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats. Clin. Exp. Nephrol. 13, 438–446 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Bankir, L. & Kriz, W. Adaptation of the kidney to protein intake and to urine concentrating activity: similar consequences in health and CRF. Kidney Int. 47, 7–24 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. Brenner, B. M. Nephron adaptation to renal injury or ablation. Am. J. Physiol. 249, F324–F337 (1985).

    CAS  PubMed  Google Scholar 

  50. Orth, S. R. & Hallan, S. I. Smoking: a risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients--absence of evidence or evidence of absence? Clin. J. Am. Soc. Nephrol. 3, 226–236 (2008).

    Article  PubMed  Google Scholar 

  51. Stack, A. G. & Murthy, B. V. Cigarette use and cardiovascular risk in chronic kidney disease: an unappreciated modifiable lifestyle risk factor. Semin. Dial. 23, 298–305 (2010).

    Article  PubMed  Google Scholar 

  52. Schaeffner, E. & Ritz, E. Alcohol and kidney damage: a Janus-faced relationship. Kidney Int. 81, 816–818 (2012).

    Article  PubMed  Google Scholar 

  53. Stookey, J. D. The diuretic effects of alcohol and caffeine and total water intake misclassification. Eur. J. Epidemiol. 15, 181–188 (1999).

    Article  CAS  PubMed  Google Scholar 

  54. Belibi, F. A. et al. Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int. 66, 964–973 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Torres, V. E. Vasopressin antagonists in polycystic kidney disease. Semin. Nephrol. 28, 306–317 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang, X., Ward, C. J., Harris, P. C. & Torres, V. E. Cyclic nucleotide signaling in polycystic kidney disease. Kidney Int. 77, 129–140 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Gattone, V. H. 2nd. Emerging therapies for polycystic kidney disease. Curr. Opin. Pharmacol. 5, 535–542 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Gross, P. Polycystic kidney disease: will it become treatable? Pol. Arch. Med. Wewn. 118, 298–301 (2008).

    PubMed  Google Scholar 

  59. Torres, V. E., Bankir, L. & Grantham, J. J. A case for water in the treatment of polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 4, 1140–1150 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Wang, X., Wu, Y., Ward, C. J., Harris, P. C. & Torres, V. E. Vasopressin directly regulates cyst growth in polycystic kidney disease. J. Am. Soc. Nephrol. 19, 102–108 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Reif, G. A. et al. Tolvaptan inhibits ERK-dependent cell proliferation, Cl(-) secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin. Am. J. Physiol. Renal Physiol. 301, F1005–F1013 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Irazabal, M. V. et al. Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease. Kidney Int. 80, 295–301 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Wang, C. J., Creed, C., Winklhofer, F. T. & Grantham, J. J. Water prescription in autosomal dominant polycystic kidney disease: a pilot study. Clin. J. Am. Soc. Nephrol. 6, 192–197 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Howl, J. et al. Characterization of the human liver vasopressin receptor. Profound differences between human and rat vasopressin-receptor-mediated responses suggest only a minor role for vasopressin in regulating human hepatic function. Biochem. J. 276, 189–195 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ostrowski, N. L. et al. Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain. Endocrinology 131, 533–535 (1992).

    Article  CAS  PubMed  Google Scholar 

  66. Serradeil-Le Gal, C. et al. Binding of [3H] SR 49059, a potent nonpeptide vasopressin V1a antagonist, to rat and human liver membranes. Biochem. Biophys. Res. Commun. 199, 353–360 (1994).

    Article  CAS  PubMed  Google Scholar 

  67. Serradeil-Le Gal, C. et al. Autoradiographic localization of vasopressin V1a receptors in the rat kidney using [3H]-SR 49059. Kidney Int. 50, 499–505 (1996).

    Article  CAS  PubMed  Google Scholar 

  68. Folny, V. et al. Pancreatic vasopressin V1b receptors: characterization in In-R1-G9 cells and localization in human pancreas. Am. J. Physiol. Endocrinol. Metab. 285, E566–E576 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Monstein, H. J., Truedsson, M., Ryberg, A. & Ohlsson, B. Vasopressin receptor mRNA expression in the human gastrointestinal tract. Eur. Surg. Res. 40, 34–40 (2008).

    Article  CAS  PubMed  Google Scholar 

  70. Oshikawa, S., Tanoue, A., Koshimizu, T. A., Kitagawa, Y. & Tsujimoto, G. Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach. Mol. Pharmacol. 65, 623–629 (2004).

    Article  CAS  PubMed  Google Scholar 

  71. Richardson, S. B., Laya, T. & VanOoy, M. Similarities between hamster pancreatic islet beta (HIT) cell vasopressin receptors and V1b receptors. J. Endocrinol. 147, 59–65 (1995).

    Article  CAS  PubMed  Google Scholar 

  72. Yibchok-Anun, S., Cheng, H., Heine, P. A. & Hsu, W. H. Characterization of receptors mediating AVP- and OT-induced glucagon release from the rat pancreas. Am. J. Physiol. 277, E56–E62 (1999).

    CAS  PubMed  Google Scholar 

  73. Hems, D. A. & Whitton, P. D. Stimulation by vasopressin of glycogen breakdown and gluconeogenesis in the perfused rat liver. Biochem. J. 136, 705–709 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Martin, G. & Baverel, G. Vasopressin promotes the metabolism of near-physiological concentration of glutamine in isolated rat liver cells. Biosci. Rep. 4, 171–176 (1984).

    Article  CAS  PubMed  Google Scholar 

  75. Whitton, P. D., Rodrigues, L. M. & Hems, D. A. Stimulation by vasopressin, angiotensin and oxytocin of gluconeogenesis in hepatocyte suspensions. Biochem. J. 176, 893–898 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Abu-Basha, E. A., Yibchok-Anun, S. & Hsu, W. H. Glucose dependency of arginine vasopressin-induced insulin and glucagon release from the perfused rat pancreas. Metabolism 51, 1184–1190 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Spruce, B. A. et al. The effect of vasopressin infusion on glucose metabolism in man. Clin. Endocrinol. (Oxf.) 22, 463–468 (1985).

    Article  CAS  Google Scholar 

  78. Aoyagi, T. et al. Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 148, 2075–2084 (2007).

    Article  CAS  PubMed  Google Scholar 

  79. Hiroyama, M. et al. Hypermetabolism of fat in V1a vasopressin receptor knockout mice. Mol. Endocrinol. 21, 247–258 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Hiroyama, M. et al. Hyperammonaemia in V1a vasopressin receptor knockout mice caused by the promoted proteolysis and reduced intrahepatic blood volume. J. Physiol. 581, 1183–1192 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zerbe, R. L., Vinicor, F. & Robertson, G. L. Plasma vasopressin in uncontrolled diabetes mellitus. Diabetes 28, 503–508 (1979).

    Article  CAS  PubMed  Google Scholar 

  82. Zerbe, R. L., Vinicor, F. & Robertson, G. L. Regulation of plasma vasopressin in insulin-dependent diabetes mellitus. Am. J. Physiol. 249, E317–E325 (1985).

    CAS  PubMed  Google Scholar 

  83. Bankir, L., Bardoux, P. & Ahloulay, M. Vasopressin and diabetes mellitus. Nephron 87, 8–18 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Ahloulay, M., Schmitt, F., Dechaux, M. & Bankir, L. Vasopressin and urinary concentrating activity in diabetes mellitus. Diabetes Metab. 25, 213–222 (1999).

    CAS  PubMed  Google Scholar 

  85. Enhörning, S. et al. Plasma copeptin, a unifying factor behind the metabolic syndrome. J. Clin. Endocrinol. Metab. 96, E1065–E1072 (2011).

    Article  PubMed  Google Scholar 

  86. Pedersen, M. M., Christiansen, J. S., Pedersen, E. B. & Mogensen, C. E. Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control. Clin. Sci. (Lond.) 83, 445–451 (1992).

    Article  CAS  Google Scholar 

  87. Thibonnier, M. et al. Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients. Hypertension 34, 1293–1300 (1999).

    Article  CAS  PubMed  Google Scholar 

  88. Thibonnier, M. et al. Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. J. Mol. Cell. Cardiol. 32, 557–564 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Bankir, L., Bichet, D. G. & Bouby, N. Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension? Am. J. Physiol. Renal Physiol. 299, F917–F928 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Nicco, C. et al. Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung. Hypertension 38, 1143–1149 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Bankir, L. Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects. Cardiovasc. Res. 51, 372–390 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Kohan, D. E. et al. Uncovering the surprising and complex roles of collecting duct adenylyl cyclases [abstract SA-OR073]. J. Am. Soc. Nephrol. 23, 82A (2012).

    Google Scholar 

  93. Blanchard, A. et al. Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent. Clin. J. Am. Soc. Nephrol. 6, 753–759 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bankir, L., Fernandes, S., Bardoux, P., Bouby, N. & Bichet, D. G. Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans. J. Am Soc. Nephrol. 16, 1920–1928 (2005).

    Article  CAS  PubMed  Google Scholar 

  95. Choukroun, G., Schmitt, F., Martinez, F., Drueke, T. B. & Bankir, L. Low urine flow reduces the capacity to excrete a sodium load in humans. Am. J. Physiol 273, R1726–R1733 (1997).

    CAS  PubMed  Google Scholar 

  96. Hall, J. E., Montani, J. P., Woods, L. L. & Mizelle, H. L. Renal escape from vasopressin: role of pressure diuresis. Am. J. Physiol. 250, F907–F916 (1986).

    Article  CAS  PubMed  Google Scholar 

  97. Bankir, L., Bardoux, P., Mayaudon, H., Dupuy, O. & Bauduceau, B. Impaired urinary flow rate during the day: a new factor possibly involved in hypertension and in the lack of nocturnal dipping [French]. Arch. Mal. Coeur Vaiss. 95, 751–754 (2002).

    CAS  PubMed  Google Scholar 

  98. Bankir, L. et al. Nighttime blood pressure and nocturnal dipping are associated with daytime urinary sodium excretion in African subjects. Hypertension 51, 891–898 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. Guerrot, D. et al. Reduced insulin secretion and nocturnal dipping of blood pressure are associated with a disturbed circadian pattern of urine excretion in metabolic syndrome. J. Clin. Endocrinol. Metab. 96, E929–E933 (2011).

    Article  CAS  PubMed  Google Scholar 

  100. Zhang, X., Hense, H. W., Riegger, G. A. & Schunkert, H. Association of arginine vasopressin and arterial blood pressure in a population-based sample. J. Hypertens. 17, 319–324 (1999).

    Article  CAS  PubMed  Google Scholar 

  101. Bakris, G., Bursztyn, M., Gavras, I., Bresnahan, M. & Gavras, H. Role of vasopressin in essential hypertension: racial differences. J. Hypertens. 15, 545–550 (1997).

    Article  CAS  PubMed  Google Scholar 

  102. Bankir, L., Perucca, J. & Weinberger, M. H. Ethnic differences in urine concentration: possible relationship to blood pressure. Clin. J. Am. Soc. Nephrol. 2, 304–312 (2007).

    Article  PubMed  Google Scholar 

  103. Cowley, A. W. Jr, Skelton, M. M. & Velasquez, M. T. Sex differences in the endocrine predictors of essential hypertension. Vasopressin versus renin. Hypertension 7, I151–I160 (1985).

    Article  PubMed  Google Scholar 

  104. Bursztyn, M., Bresnahan, M., Gavras, I. & Gavras, H. Pressor hormones in elderly hypertensive persons. Racial differences. Hypertension 15, I88–I92 (1990).

    Article  CAS  PubMed  Google Scholar 

  105. Luft, F. C. Vasopressin, urine concentration, and hypertension: a new perspective on an old story. Clin. J. Am. Soc. Nephrol. 2, 196–197 (2007).

    Article  PubMed  Google Scholar 

  106. Young, J. H. et al. Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion. PLoS Genet. 1, e82 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ammar, A., Roseau, S. & Butlen, D. Pharmacological characterization of V1a vasopressin receptors in the rat cortical collecting duct. Am. J. Physiol. 262, F546–F553 (1992).

    Article  CAS  PubMed  Google Scholar 

  108. Arpin-Bott, M. P. et al. Historadioautographic localization of oxytocin and V1a vasopressin binding sites in the kidney of developing and adult rabbit, mouse and merione and of adult human. Exp. Nephrol. 10, 196–208 (2002).

    Article  CAS  PubMed  Google Scholar 

  109. Inoue, T., Nonoguchi, H. & Tomita, K. Physiological effects of vasopressin and atrial natriuretic peptide in the collecting duct. Cardiovasc. Res. 51, 470–480 (2001).

    Article  CAS  PubMed  Google Scholar 

  110. Terada, Y., Tomita, K., Nonoguchi, H., Yang, T. & Marumo, F. Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction. J. Clin. Invest. 92, 2339–2345 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kirschenbaum, M. A., Lowe, A. G., Trizna, W. & Fine, L. G. Regulation of vasopressin action by prostaglandins. Evidence for prostaglandin synthesis in the rabbit cortical collecting tubule. J. Clin. Invest. 70, 1193–1204 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Bonvalet, J. P., Pradelles, P. & Farman, N. Segmental synthesis and actions of prostaglandins along the nephron. Am. J. Physiol. 253, F377–F387 (1987).

    CAS  PubMed  Google Scholar 

  113. Schlondorff, D. Renal prostaglandin synthesis. Sites of production and specific actions of prostaglandins. Am. J. Med. 81, 1–11 (1986).

    Article  CAS  PubMed  Google Scholar 

  114. Zhang, M. Z., Sanchez Lopez, P., McKanna, J. A. & Harris, R. C. Regulation of cyclooxygenase expression by vasopressin in rat renal medulla. Endocrinology 145, 1402–1409 (2004).

    Article  CAS  PubMed  Google Scholar 

  115. Perucca, J., Bichet, D. G., Bardoux, P., Bouby, N. & Bankir, L. Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists. J. Am. Soc. Nephrol. 19, 1721–1731 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Izumi, Y. et al. Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway. Am. J. Physiol. Renal Physiol. 292, F1418–F1426 (2007).

    Article  CAS  PubMed  Google Scholar 

  117. Balment, R. J., Brimble, M. J., Forsling, M. L. & Musabayane, C. T. Natriuretic response of the rat to plasma concentrations of arginine vasopressin within the physiological range. J. Physiol. 352, 517–526 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Ando, Y. & Asano, Y. Functional evidence for an apical V1 receptor in rabbit cortical collecting duct. Am. J. Physiol. 264, F467–F471 (1993).

    CAS  PubMed  Google Scholar 

  119. Ando, Y., Tabei, K. & Asano, Y. Luminal vasopressin modulates transport in the rabbit cortical collecting duct. J. Clin. Invest. 88, 952–959 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ikeda, M., Yoshitomi, K., Imai, M. & Kurokawa, K. Cell Ca2+ response to luminal vasopressin in cortical collecting tubule principal cells. Kidney Int. 45, 811–816 (1994).

    Article  CAS  PubMed  Google Scholar 

  121. Loichot, C. et al. Vasopressin does not effect hypertension caused by long-term nitric oxide inhibition. Hypertension 35, 602–608 (2000).

    Article  CAS  PubMed  Google Scholar 

  122. Nonoguchi, H. et al. Role of urinary arginine vasopressin in the sodium excretion in patients with chronic renal failure. Am. J. Med Sci. 312, 195–201 (1996).

    Article  CAS  PubMed  Google Scholar 

  123. Crofton, J. T., Dustan, H., Share, L. & Brooks, D. P. Vasopressin secretion in normotensive black and white men and women on normal and low sodium diets. J. Endocrinol. 108, 191–199 (1986).

    Article  CAS  PubMed  Google Scholar 

  124. Wang, Y. X., Crofton, J. T. & Share, L. Sex differences in the cardiovascular and renal actions of vasopressin in conscious rats. Am. J. Physiol. 272, R370–R376 (1997).

    CAS  PubMed  Google Scholar 

  125. Bhandari, S. S. et al. Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin. Sci. (Lond.) 116, 257–263 (2009).

    Article  CAS  Google Scholar 

  126. Share, L., Crofton, J. T. & Ouchi, Y. Vasopressin: sexual dimorphism in secretion, cardiovascular actions and hypertension. Am. J. Med. Sci. 295, 314–319 (1988).

    Article  CAS  PubMed  Google Scholar 

  127. Stachenfeld, N. S., Splenser, A. E., Calzone, W. L., Taylor, M. P. & Keefe, D. L. Sex differences in osmotic regulation of AVP and renal sodium handling. J. Appl. Physiol. 91, 1893–1901 (2001).

    Article  CAS  PubMed  Google Scholar 

  128. Perucca, J., Bouby, N., Valeix, P. & Bankir, L. Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R700–R705 (2007).

    Article  CAS  PubMed  Google Scholar 

  129. O'Donnell, C. J. et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 97, 1766–1772 (1998).

    Article  CAS  PubMed  Google Scholar 

  130. Rankinen, T. et al. AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study. Am. J. Physiol. Heart Circ. Physiol. 279, H368–H374 (2000).

    Article  CAS  PubMed  Google Scholar 

  131. Stankovic, A., Zivkovic, M. & Alavantic, D. Angiotensin I-converting enzyme gene polymorphism in a Serbian population: a gender-specific association with hypertension. Scand. J. Clin. Lab. Invest 62, 469–475 (2002).

    Article  CAS  PubMed  Google Scholar 

  132. Wang, J. G. et al. Association between hypertension and variation in the alpha- and beta-adducin genes in a white population. Kidney Int. 62, 2152–2159 (2002).

    Article  CAS  PubMed  Google Scholar 

  133. Chassin, C. et al. Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin. J. Exp. Med. 204, 2837–2852 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Bolignano, D. et al. Aquaretic inhibits renal cancer proliferation: Role of vasopressin receptor-2 (V2-R). Urol. Oncol. 28, 642–647 (2010).

    Article  CAS  PubMed  Google Scholar 

  135. Braver, D. J., Modan, M., Chetrit, A., Lusky, A. & Braf, Z. Drinking, micturition habits, and urine concentration as potential risk factors in urinary bladder cancer. J. Natl Cancer Inst. 78, 437–440 (1987).

    CAS  PubMed  Google Scholar 

  136. Tang, C. et al. Downregulation of Klotho expression by dehydration. Am. J. Physiol. Renal Physiol. 301, F745–F750 (2011).

    Article  CAS  PubMed  Google Scholar 

  137. Ganio, M. S. et al. Mild dehydration impairs cognitive performance and mood of men. Br. J. Nutr. 106, 1535–1543 (2011).

    Article  CAS  PubMed  Google Scholar 

  138. Benton, D. Dehydration influences mood and cognition: a plausible hypothesis? Nutrients 3, 555–573 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Adan, A. Cognitive performance and dehydration. J. Am. Coll. Nutr. 31, 71–78 (2012).

    Article  PubMed  Google Scholar 

  140. Armstrong, L. E. et al. Mild dehydration affects mood in healthy young women. J. Nutr. 142, 382–388 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Patel, A. V., Mihalik, J. P., Notebaert, A. J., Guskiewicz, K. M. & Prentice, W. E. Neuropsychological performance, postural stability, and symptoms after dehydration. J. Athl. Train. 42, 66–75 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Spigt, M. G. et al. Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial. Eur. J. Neurol. 12, 715–718 (2005).

    Article  CAS  PubMed  Google Scholar 

  143. Stookey, J. D., Purser, J. L., Pieper, C. F. & Cohen, H. J. Plasma hypertonicity: another marker of frailty? J. Am. Geriatr. Soc. 52, 1313–1320 (2004).

    Article  PubMed  Google Scholar 

  144. Wilson, M. M. & Morley, J. E. Impaired cognitive function and mental performance in mild dehydration. Eur. J. Clin. Nutr. 57 (Suppl. 2), S24–S29 (2003).

    Article  PubMed  Google Scholar 

  145. Spigt, M. G., Knottnerus, J. A., Westerterp, K. R., Olde Rikkert, M. G. & Schayck, C. P. The effects of 6 months of increased water intake on blood sodium, glomerular filtration rate, blood pressure, and quality of life in elderly (aged 55–75) men. J. Am. Geriatr. Soc. 54, 438–443 (2006).

    Article  PubMed  Google Scholar 

  146. Edmonds, C. J. & Jeffes, B. Does having a drink help you think? 6-7-Year-old children show improvements in cognitive performance from baseline to test after having a drink of water. Appetite 53, 469–472 (2009).

    Article  PubMed  Google Scholar 

  147. Bichet, D. G. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin. Nephrol. 28, 245–251 (2008).

    Article  CAS  PubMed  Google Scholar 

  148. Mizuno, J. & Takeda, N. Phylogenetic study of the arginine-vasotocin/arginine-vasopressin-like immunoreactive system in invertebrates. Comp. Biochem. Physiol. A Comp. Physiol. 91, 739–747 (1988).

    Article  CAS  PubMed  Google Scholar 

  149. Kawada, T., Kanda, A., Minakata, H., Matsushima, O. & Satake, H. Identification of a novel receptor for an invertebrate oxytocin/vasopressin superfamily peptide: molecular and functional evolution of the oxytocin/vasopressin superfamily. Biochem. J. 382, 231–237 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Stafflinger, E. et al. Cloning and identification of an oxytocin/vasopressin-like receptor and its ligand from insects. Proc. Natl Acad. Sci. USA 105, 3262–3267 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  151. van Kesteren, R. E. et al. Evolution of the vasopressin/oxytocin superfamily: characterization of a cDNA encoding a vasopressin-related precursor, preproconopressin, from the mollusc Lymnaea stagnalis. Proc. Natl Acad. Sci. USA 89, 4593–4597 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Zerbe, R. L. & Robertson, G. L. Osmoregulation of thirst and vasopressin secretion in human subjects: effect of various solutes. Am. J. Physiol. 244, E607–E614 (1983).

    CAS  PubMed  Google Scholar 

  153. Baylis, P. H. Osmoregulation and control of vasopressin secretion in healthy humans. Am. J. Physiol. 253, R671–R678 (1987).

    CAS  PubMed  Google Scholar 

  154. Galanth, C., Hus-Citharel, A., Li, B. & Llorens-Cortes, C. Apelin in the control of body fluid homeostasis and cardiovascular functions. Curr. Pharm. Des. 18, 789–798 (2012).

    Article  CAS  PubMed  Google Scholar 

  155. Ramsay, D. J. The importance of thirst in maintenance of fluid balance. Baillieres Clin. Endocrinol. Metab. 3, 371–391 (1989).

    Article  CAS  PubMed  Google Scholar 

  156. Zerbe, R. L., Miller, J. Z. & Robertson, G. L. The reproducibility and heritability of individual differences in osmoregulatory function in normal human subjects. J. Lab. Clin. Med. 117, 51–59 (1991).

    CAS  PubMed  Google Scholar 

  157. Perrier, E. et al. Hydration biomarkers in free-living adults with different levels of habitual fluid consumption. Br. J. Nutr. 1–10 (2012).

  158. Andersen, L. J., Andersen, J. L., Schutten, H. J., Warberg, J. & Bie, P. Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans. Am. J. Physiol. 259, R53–R60 (1990).

    CAS  PubMed  Google Scholar 

  159. Robertson, G. L. The regulation of vasopressin function in health and disease. Recent Prog. Horm. Res. 33, 333–385 (1976).

    CAS  PubMed  Google Scholar 

  160. Schmitt, F. et al. Influence of plasma amino acid level on vasopressin secretion. Diabetes Metab. 29, 352–361 (2003).

    Article  CAS  PubMed  Google Scholar 

  161. Bichet, D. G., Arthus, M. F., Barjon, J. N., Lonergan, M. & Kortas, C. Human platelet fraction arginine-vasopressin. Potential physiological role. J. Clin. Invest. 79, 881–887 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Morgenthaler, N. G., Struck, J., Jochberger, S. & Dunser, M. W. Copeptin: clinical use of a new biomarker. Trends Endocrinol. Metab. 19, 43–49 (2008).

    Article  CAS  PubMed  Google Scholar 

  163. Fenske, W. et al. Copeptin levels associate with cardiovascular events in patients with ESRD and type 2 diabetes mellitus. J. Am. Soc. Nephrol. 22, 782–790 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Howl, J. & Wheatley, M. Molecular pharmacology of V1a vasopressin receptors. Gen. Pharmacol. 26, 1143–1152 (1995).

    Article  CAS  PubMed  Google Scholar 

  165. Jard, S. Vasopressin receptors. A historical survey. Adv. Exp. Med. Biol. 449, 1–13 (1998).

    Article  CAS  PubMed  Google Scholar 

  166. Walum, H. et al. Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proc. Natl Acad. Sci. USA 105, 14153–14156 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Koshimizu, T. A. et al. Vasopressin V1a and V1b receptors: from molecules to physiological systems. Physiol. Rev. 92, 1813–1864 (2012).

    Article  CAS  PubMed  Google Scholar 

  168. Akerlund, M. et al. Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women. Br. J. Obstet. Gynaecol. 106, 1047–1053 (1999).

    Article  PubMed  Google Scholar 

  169. Grazzini, E. et al. Vasopressin regulates adrenal functions by acting through different vasopressin receptor subtypes. Adv. Exp. Med. Biol. 449, 325–334 (1998).

    Article  CAS  PubMed  Google Scholar 

  170. Thibonnier, M., Snajdar, R. M. & Rapp, J. P. Characterization of vasopressin receptors of rat urinary bladder and spleen. Am. J. Physiol. 251, H115–H120 (1986).

    Article  CAS  PubMed  Google Scholar 

  171. Manning, M., Lowbridge, J., Haldar, J. & Sawyer, W. H. Design of neurohypophyseal peptides that exhibit selective agonistic and antagonistic properties. Fed. Proc. 36, 1848–1852 (1977).

    CAS  PubMed  Google Scholar 

  172. Manning, M. & Sawyer, W. H. Design, synthesis and some uses of receptor-specific agonists and antagonists of vasopressin and oxytocin. J. Recept. Res. 13, 195–214 (1993).

    Article  CAS  PubMed  Google Scholar 

  173. Kinter, L. B., Huffman, W. F. & Stassen, F. L. Antagonists of the antidiuretic activity of vasopressin. Am. J. Physiol. 254, F165–F177 (1988).

    Article  CAS  PubMed  Google Scholar 

  174. Richardson, D. W. & Robinson, A. G. Desmopressin. Ann. Intern. Med. 103, 228–239 (1985).

    Article  CAS  PubMed  Google Scholar 

  175. Saito, M., Tahara, A. & Sugimoto, T. 1-desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1b vasopressin receptor. Biochem. Pharmacol. 53, 1711–1717 (1997).

    Article  CAS  PubMed  Google Scholar 

  176. Krag, A., Borup, T., Moller, S. & Bendtsen, F. Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome. Adv. Ther. 25, 1105–1140 (2008).

    Article  PubMed  Google Scholar 

  177. Lebrec, D. Review article: future indications for terlipressin therapy. Aliment. Pharmacol. Ther. 20 (Suppl. 3), 65–67 (2004).

    Article  CAS  PubMed  Google Scholar 

  178. Krag, A., Bendtsen, F., Pedersen, E. B., Holstein-Rathlou, N. H. & Moller, S. Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects. Am. J. Physiol. Renal Physiol. 295, F1295–F1300 (2008).

    Article  CAS  PubMed  Google Scholar 

  179. Krag, A., Pedersen, E. B., Moller, S. & Bendtsen, F. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention. Scand. J. Clin. Lab. Invest. 71, 112–116 (2011).

    Article  CAS  PubMed  Google Scholar 

  180. Schrier, R. W. et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N. Engl. J. Med. 355, 2099–2112 (2006).

    Article  CAS  PubMed  Google Scholar 

  181. Palm, C., Pistrosch, F., Herbrig, K. & Gross, P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am. J. Med. 119, S87–S92 (2006).

    Article  CAS  PubMed  Google Scholar 

  182. Verbalis, J. G. AVP receptor antagonists as aquaretics: review and assessment of clinical data. Cleve. Clin. J. Med. 73 (Suppl. 3), S24–S33 (2006).

    Article  PubMed  Google Scholar 

  183. Farmakis, D., Filippatos, G., Kremastinos, D. T. & Gheorghiade, M. Vasopressin and vasopressin antagonists in heart failure and hyponatremia. Curr. Heart Fail. Rep. 5, 91–96 (2008).

    Article  CAS  PubMed  Google Scholar 

  184. Aperis, G. & Alivanis, P. Tolvaptan: a new therapeutic agent. Rev. Recent Clin. Trials 6, 177–188 (2011).

    Article  CAS  PubMed  Google Scholar 

  185. Ferguson-Myrthil, N. Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan. Cardiol. Rev. 18, 313–321 (2010).

    Article  PubMed  Google Scholar 

  186. Goldsmith, S. R. Is there a cardiovascular rationale for the use of combined vasopressin V1a/V2 receptor antagonists? Am. J. Med. 119, S93–S96 (2006).

    Article  CAS  PubMed  Google Scholar 

  187. Bankir, L. & Trinh-Trang-Tan, M. M. Urea and the kidney in The Kidney 6th edn (ed. Brenner, B. M.) 637–679 (W. B. Saunders Company, Philadelphia, 2000).

    Google Scholar 

  188. Bouby, N. et al. Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action. J. Am. Soc. Nephrol. 7, 842–851 (1996).

    CAS  PubMed  Google Scholar 

  189. Capasso, G. et al. A decrease in renal medullary tonicity stimulates anion transport in Henle's loop of rat kidneys. Am. J. Physiol. 274, F693–F699 (1998).

    CAS  PubMed  Google Scholar 

  190. Bankir, L., Martin, H. & Bouby, N. Vasopressin (AVP) increases GFR in rats. Disclosure of this effect was previously obscured by inadequate experimental protocols. FASEB J. 12, A331 (1998).

    Google Scholar 

  191. Roald, A. B., Tenstad, O. & Aukland, K. The effect of AVP-V2 receptor stimulation on local GFR in the rat kidney. Acta Physiol. Scand. 168, 351–359 (2000).

    Article  CAS  PubMed  Google Scholar 

  192. Trinh-Trang-Tan, M. M., Bouby, N., Doute, M. & Bankir, L. Effect of long- and short-term antidiuretic hormone availability on internephron heterogeneity in the adult rat. Am. J. Physiol. 246, F879–F888 (1984).

    CAS  PubMed  Google Scholar 

  193. Bankir, L. et al. Adaptation of the rat kidney to altered water intake and urine concentration. Pflugers Arch. 412, 42–53 (1988).

    Article  CAS  PubMed  Google Scholar 

  194. Anastasio, P. et al. Level of hydration and renal function in healthy humans. Kidney Int. 60, 748–756 (2001).

    Article  CAS  PubMed  Google Scholar 

  195. Hadj-Aissa, A. et al. Influence of the level of hydration on the renal response to a protein meal. Kidney Int. 42, 1207–1216 (1992).

    Article  CAS  PubMed  Google Scholar 

  196. Boertien, W. E. et al. Short-term renal hemodynamic responses and safety of tolvaptan in subjects with ADPKD at various levels of kidney function. [Abstract TH-PO632]. J. Am. Soc. Nephrol. 23, 243A (2012).

    Google Scholar 

  197. Bangalore, S. et al. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur. Heart J. 31, 2897–2908 (2010).

    Article  CAS  PubMed  Google Scholar 

  198. Filippone, E. J. & Foy, A. The j-curve revisited: a therapeutic dilemma. Cardiol. Rev. 20, 253–258 (2012).

    Article  PubMed  Google Scholar 

  199. Berl, T. Impact of solute intake on urine flow and water excretion. J. Am. Soc. Nephrol. 19, 1076–1078 (2008).

    Article  CAS  PubMed  Google Scholar 

  200. Epstein, F. H., Kleeman, C. R. & Hendrikx, A. The influence of bodily hydration on the renal concentrating process. J. Clin. Invest. 36, 629–634 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Yang, B. & Bankir, L. Urea and urine concentrating ability: new insights from studies in mice. Am. J. Physiol. Renal Physiol. 288, F881–F896 (2005).

    Article  CAS  PubMed  Google Scholar 

  202. Fenton, R. A. Essential role of vasopressin-regulated urea transport processes in the mammalian kidney. Pflugers Arch. 458, 169–177 (2009).

    Article  CAS  PubMed  Google Scholar 

  203. Armsen, T., Glossmann, V., Weinzierl, M. & Edel, H. H. Familial proximal tubular azotemia. Elevated urea plasma levels in normal kidney function [German]. Dtsch. Med. Wochenschr. 111, 702–706 (1986).

    Article  CAS  PubMed  Google Scholar 

  204. Bankir, L. et al. Is the process of urinary urea concentration responsible for a high glomerular filtration rate? J. Am. Soc. Nephrol. 4, 1091–1103 (1993).

    CAS  PubMed  Google Scholar 

  205. Bankir, L., Bouby, N., Trinh-Trang-Tan, M. M., Ahloulay, M. & Promeneur, D. Direct and indirect cost of urea excretion. Kidney Int. 49, 1598–1607 (1996).

    Article  CAS  PubMed  Google Scholar 

  206. D'Apolito, M. et al. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. J. Clin. Invest. 120, 203–213 (2010).

    Article  PubMed  Google Scholar 

  207. Kraus, L. M. & Kraus, A. P. Jr. Carbamoylation of amino acids and proteins in uremia. Kidney. Int. Suppl. 78, S102–S107 (2001).

    Article  CAS  PubMed  Google Scholar 

  208. Vaziri, N. D., Gandotra, G., Moradi, H. & Yuan, J. Central role of urea in disruption of intestinal tight junction and barrier dysfunction in CKD. [Abstract FR-PO628]. J. Am. Soc. Nephrol. 23, 514A (2012).

    Google Scholar 

  209. Bankir, L. & Yang, B. New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism. Kidney Int. 81, 1179–1198 (2012).

    Article  CAS  PubMed  Google Scholar 

  210. Hauben, D. J., Le Roith, D., Glick, S. M. & Mahler, D. Nonoliguric vasopressin oversecretion in severely burned patients. Isr. J. Med. Sci. 16, 101–105 (1980).

    CAS  PubMed  Google Scholar 

  211. Loirat, P. et al. Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin. N. Engl. J. Med. 299, 915–919 (1978).

    Article  CAS  PubMed  Google Scholar 

  212. Shirani, K. Z. et al. Inappropriate vasopressin secretion (SIADH) in burned patients. J. Trauma 23, 217–224 (1983).

    Article  CAS  PubMed  Google Scholar 

  213. Walsh, C. H., Baylis, P. H. & Malins, J. M. Plasma arginine vasopressin in diabetic ketoacidosis. Diabetologia 16, 93–96 (1979).

    Article  CAS  PubMed  Google Scholar 

  214. Vokes, T. P., Aycinena, P. R. & Robertson, G. L. Effect of insulin on osmoregulation of vasopressin. Am. J. Physiol. 252, E538–E548 (1987).

    CAS  PubMed  Google Scholar 

  215. Roch-Ramel, F., Diezi, J., Chomety, F., Michoud, P. & Peters, G. Disposal of large urea overloads by the rat kidney: a micropuncture study. Am. J. Physiol. 218, 1524–1532 (1970).

    Article  CAS  PubMed  Google Scholar 

  216. Addis, T. The osmotic work of the kidney and the treatment of glomerular nephritis. Trans. Assoc. Am. Phys. 55, 223–229 (1940).

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Maurice Laville (Nephrology Department, Edouard–Herriot Hospital, Claude Bernard University, Lyon, France) and Pascal Houillier (Renal and Metabolic Diseases Unit, Georges Pompidou Hospital and Paris–Descartes University, Paris, France) for providing valuable advice on this Review. Lise Bankir thanks all her collaborators who have participated in her studies on the potential adverse effects of vasopressin over the past 20 years, and the clinicians (in particular, Paul Jungers, Paris, and Daniel Bichet, Montreal) who have encouraged her in these studies.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed equally to researching data for the article and to discussions of the content. L. Bankir and E. Ritz wrote the article and L. Bankir reviewed/edited it before submission.

Corresponding author

Correspondence to Lise Bankir.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Sites of expression of vasopressin receptors in the kidney, their functional relevance and potential adverse effects (PDF 87 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bankir, L., Bouby, N. & Ritz, E. Vasopressin: a novel target for the prevention and retardation of kidney disease?. Nat Rev Nephrol 9, 223–239 (2013). https://doi.org/10.1038/nrneph.2013.22

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2013.22

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing