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07.06.2016

Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats

verfasst von: Maylla Ronacher Simões, Silvio César Preti, Bruna Fernandes Azevedo, Jonaína Fiorim, David D. Freire Jr., Emilia Polaco Covre, Dalton Valentim Vassallo, Leonardo dos Santos

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2017

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Abstract

Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30 days (first dose 4 µg/100 g followed by 0.05 µg/100 g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance.

Patrick, L. (2006). Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Alternative Medicine Review, 11(1), 2–22.PubMed

Roncal, C., Mu, W., Reungjui, S., Kim, K. M., Henderson, G. N., Ouyang, X., et al. (2007). Lead, at low levels, accelerates arteriolopathy and tubulointerstitial injury in chronic kidney disease. American Journal of Physiology. Renal Physiology, 293(4), F1391–F1396.CrossRefPubMed

Fioresi, M., Simões, M. R., Furieri, L. B., Broseghini-Filho, G. B., Vescovi, M. V., Stefanon, I., & Vassallo, D. V. (2014). Chronic lead exposure increases blood pressure and myocardial contractility in rats. PLoS One, 9(5), e96900.CrossRefPubMedPubMedCentral

ATSDR (Agency for Toxic Substances and Disease Registry). (2005). Toxicological profile for lead. Annual report. Atlanta: Department of Health and Human Services, Public Health Service.

Den, H. E., Nawrot, T., & Staessen, J. A. (2002). The relationship between blood pressure and blood lead in NHANES III. National Health and Nutritional Examination Survey. Journal of Human Hypertension, 16, 563–568.CrossRef

Vupputuri, S., He, J., Muntner, P., Bazzano, L. A., Whelton, P. K., & Batuman, V. (2003). Blood lead level is associated with elevated blood pressure in blacks. Hypertension, 41, 463–468.CrossRefPubMed

Silveira, E. A., Siman, F. D., de Oliveira Faria, T., Vescovi, M. V., Furieri, L. B., Lizardo, J. H., et al. (2014). Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas. Free Radical Biology and Medicine, 67, 366–376.CrossRefPubMed

Nunes, K. Z., Nunes, D. O., Silveira, E. A., Cruz Pereira, C. A., Broseghini Filho, G. B., Vassallo, D. V., & Fioresi, M. (2015). Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide. PLoS One, 10(3), e0120965.CrossRefPubMedPubMedCentral

Simões, M. R., Aguado, A., Fiorim, J., Silveira, E. A., Azevedo, B. F., Toscano, C. M., et al. (2015). MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways. Toxicology and Applied Pharmacology, 283(2), 127–138.CrossRefPubMed

10.

Gonick, H. C., Ding, Y., Bondy, S. C., Ni, Z., & Vaziri, N. D. (1997). Lead-induced hypertension: Interplay of nitric oxide and reactive oxygen species. Hypertension, 30(6), 1487–1492.CrossRefPubMed

11.

Khalil-Manesh, F., Gonick, H. C., Weiler, E. W., Prins, B., Weber, M. A., & Purdy, R. E. (1993). Lead-induced hypertension: Possible role of endothelial factors. American Journal of Hypertension, 6(9), 723–729.CrossRefPubMed

12.

Vaziri, N. D., Liang, K., & Ding, Y. (1999). Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension. Kidney International, 56(4), 1492–1498.CrossRefPubMed

13.

Simões, M. R., Ribeiro Júnior, R. F., Vescovi, M. V., de Jesus, H. C., Padilha, A. S., Stefanon, I., et al. (2011). Acute lead exposure increases arterial pressure: Role of the renin-angiotensin system. PLoS One, 6(4), e18730.CrossRefPubMedPubMedCentral

14.

Tsao, D. A., Yu, H. S., Cheng, J. T., Ho, C. K., & Chang, H. R. (2000). The change of beta-adrenergic system in lead-induced hypertension. Toxicology and Applied Pharmacology, 164(2), 127–133.CrossRefPubMed

15.

Moreira, F. R., & Moreira, J. C. (2004). Effects of lead exposure on the human body and health implications. Revista Panamericana de Salud Pública, 15(2), 119–129.CrossRefPubMed

16.

Stewart, W. F., Schwartz, B. S., Simon, D., Kelsey, K., & Todd, A. C. (2002). ApoE genotype, past adult lead exposure, and neurobehavioral function. Environmental Health Perspectives, 110(5), 501–505.CrossRefPubMedPubMedCentral

17.

Poręba, R., Poręba, M., Gać, P., Steinmetz-Beck, A., Beck, B., Pilecki, W., et al. (2011). Electrocardiographic changes in workers occupationally exposed to lead. Annals of Noninvasive Electrocardiology, 16(1), 33–40.CrossRefPubMed

18.

Jhun, H. J., Kim, H., & Paek, D. M. (2005). The association between blood metal concentrations and heart rate variability: A crosssectional study. International Archives of Occupational and Environmental Health, 78, 243–247.CrossRefPubMed

19.

Carmignani, M., Volpe, A. R., Boscolo, P., Qiao, N., Di Gioacchino, M., Grilli, A., & Felaco, M. (2000). Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment. Life Sciences, 68(4), 401–415.CrossRefPubMed

20.

Vasquez, E. C., Meyrelles, S. S., Mauad, H., & Cabral, A. M. (1997). Neural reflex regulation of arterial pressure in pathophysiological conditions: Interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex. Brazilian Journal of Medical and Biological Research, 30(4), 521–532.CrossRefPubMed

21.

Peotta, V. A., Vasquez, E. C., & Meyrelles, S. S. (2001). Cardiovascular neural reflexes in L-NAME-induced hypertension in mice. Hypertension, 38, 555–559.CrossRefPubMed

22.

Lacerda, J. E., Consolim-Colombo, F. M., Moreira, E. D., Ida, F., Silva, G. J., Irigoyen, M. C., & Krieger, E. M. (2007). Influence of cardiopulmonary reflex on the sympathetic activity during myocardial infarction. Autonomic Neuroscience, 133(2), 128–135.CrossRefPubMed

23.

Lee, H. B., & Blaufox, M. D. (1985). Blood volume in the rat. Journal of Nuclear Medicine, 26(1), 72–76.PubMed

24.

Fiorim, J., Ribeiro Junior, R. F., Silveira, E. A., Padilha, A. S., Vescovi, M. V., de Jesus, H. C., et al. (2011). Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas. PLoS One, 6(2), e17117.CrossRefPubMedPubMedCentral

25.

Oliveira, L. R., de Melo, V. U., Macedo, F. N., Barreto, A. S., Badaue-Passos, D, Jr., Viana dos Santos, M. R., et al. (2012). Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats. Autonomic Neuroscience, 167, 45–49.CrossRefPubMedPubMedCentral

26.

Fazan, R, Jr., de Oliveira, M., Oliveira, J. A., Salgado, H. C., & Garcia-Cairasco, N. (2011). Changes in autonomic control of the cardiovascular system in the Wistar audiogenic rat (WAR) strain. Epilepsy & Behavior, 22, 666–670.CrossRef

27.

Sharp, D. S., Becker, C. E., & Smith, A. H. (1987). Chronic low-level lead exposure. Its role in the pathogenesis of hypertension. Medical Toxicology, 2(3), 210–232.CrossRefPubMed

28.

Hertz-Picciotto, I., & Croft, J. (1993). Review of the relation between blood lead and blood pressure. Epidemiologic Reviews, 15(2), 352–373.CrossRefPubMed

29.

Silveira, E. A., Lizardo, J. H., Souza, L. P., Stefanon, I., & Vassallo, D. V. (2010). Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent. Brazilian Journal of Medical and Biological Research, 43(5), 492–499.CrossRefPubMed

30.

Lai, C. C., Lin, H. H., Chen, C. W., Chen, S. H., & Chiu, T. H. (2002). Excitatory action of lead on rat sympathetic preganglionic neurons in vitro and in vivo. Life Sciences, 71(9), 1035–1045.CrossRefPubMed

31.

Chapleau, M. W., Li, Z., Meyrelles, S. S., Ma, X., & Abboud, F. M. (2001). Mechanisms determining sensitivity of baroreceptor afferents in health and disease. Annals of the New York Academy of Sciences, 940, 1–19.CrossRefPubMed

32.

Lanfranchi, P. A., & Somers, V. K. (2002). Arterial baroreflex function and cardiovascular variability: interactions and implications. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 283, R815–R826.CrossRefPubMed

33.

Weston, P. J., Panerai, R. B., McCullough, A., McNally, P. G., James, M. A., Potter, J. F., et al. (1996). Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index. Diabetologia, 39, 1385–1391.CrossRefPubMed

34.

Parati, G., & Esler, M. (2012). The human sympathetic nervous system: Its relevance in hypertension and heart failure. European Heart Journal, 33, 1058–1066.CrossRefPubMed

35.

Cardoso, L. M., Fernandes, L. G., Alves, A. M., Pedrosa, M. L., Silva, M. E., Colombari, E., et al. (2007). Cardiopulmonary reflex is attenuated in iron overload conscious rats. Nutritional Neuroscience, 10(3–4), 121–128.CrossRefPubMed

36.

Carmignani, M., Finelli, V. N., & Boscolo, P. (1983). Mechanisms in cardiovascular regulation following chronic exposure of male rats to inorganic mercury. Toxicology and Applied Pharmacology, 69(3), 442–450.CrossRefPubMed

37.

Germanó, D., Pochiero, M., Romeo, G., Nunziata, A., Costa, G., & Caputi, A. P. (1984). Cadmium alters arterial baroreflex control of heart rate in the conscious rat. Archives of Toxicology, 7, 374–377.CrossRefPubMed

38.

Boscolo, P., & Carmignani, M. (1988). Neurohumoral blood pressure regulation in lead exposure. Environmental Health Perspectives, 78, 101–106.CrossRefPubMedPubMedCentral

39.

Iannaccone, A., Boscolo, P., & Carmignani, M. (1981). Neurogenic and humoral mechanisms in arterial hypertension of chronically lead-exposed rats. Medicina del Lavoro, 72, 13–21.PubMed

40.

Carmignani, M., Boscolo, P., Marchetti, P., & Iannaccone, A. (1980). Neurogenic components in cardiovascular reactivity of chronically lead-exposed rats. Developments in Toxicology and Environmental Science, 8, 595–598.PubMed

41.

Casadei, B., & Paterson, D. J. (2000). Should we still use nitrovasodilators to test baroreflex sensitivity? Journal of Hypertension, 18(1), 3–6.CrossRefPubMed

42.

Sener, A., & Smith, F. G. (2001). Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner. American Journal of Physiology Heart and Circulatory Physiology, 280(5), H2255–H2263.PubMed

43.

Schwarz, P., Diem, R., Dun, N. J., & Forstermann, U. (1995). Endogenous and exogenous nitric oxide inhibits norepinephrine release from rat heart sympathetic nerves. Circulation Research, 77, 841–848.CrossRefPubMed

44.

Reddy, G. R., Davi, B. C., & Chetty, C. S. (2007). Developmental lead neurotoxicity: Alterations in brain cholinergic system. Neurotoxicology, 28(2), 402–407.CrossRefPubMed

45.

Borisova, T., Krisanova, N., Sivko, R., Kasatkina, L., Borysov, A., Griffin, S., & Wireman, M. (2011). Presynaptic malfunction: The neurotoxic effects of cadmium and lead on the proton gradient of synaptic vesicles and glutamate transport. Neurochemistry International, 59(2), 272–279.CrossRefPubMed

46.

Averill, D. B., & Diz, D. I. (2000). Angiotensin peptides and the baroreflex control of sympathetic outflow: Pathways and mechanisms of the medulla oblongata. Brain Research Bulletin, 51(2), 119–128.CrossRefPubMed

47.

Phillips, M. I., & Sumners, C. (1998). Angiotensin II in central nervous system physiology. Regulatory Peptides, 78, 1–11.CrossRefPubMed

48.

Carmignani, M., Boscolo, P., Poma, A., & Volpe, A. R. (1999). Kininergic system and arterial HTN following chronic exposure to inorganic lead. Immunopharmacology, 44, 105–110.CrossRefPubMed

49.

Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. (1996). Heart rate variability: Standards of measurement, physiologic interpretation and clinical use. Circulation, 93, 1043–1065.CrossRef

50.

Malliani, A., Lombardi, F., & Pagani, M. (1994). Power spectrum analysis of heart rate variability: A tool to explore neural regulatory mechanisms. British Heart Journal, 71, 1–2.CrossRefPubMedPubMedCentral

51.

Feng, W., He, X., Chen, M., Deng, S., Qiu, G., Li, X., et al. (2015). Urinary metals and heart rate variability: A cross-sectional study of urban adults in Wuhan. China. Environmental Health Perspectives, 123(3), 217–222.PubMed

52.

Böckelmann, I., Pfister, E., & Darius, S. (2011). Early effects of long-term neurotoxic lead exposure in copper works employees. Journal of Toxicology, 2011, 832519.CrossRefPubMedPubMedCentral

53.

Moraes, O. A., Colucci, J. A., Souza, L. E., Scapini, K. B., Moraes-Silva, I. C., Mostarda, C., et al. (2013). Cardiovascular autonomic dysfunction in non-obese diabetic mice. Autonomic Neuroscience, 177, 143–147.CrossRefPubMed

54.

Presciuttini, B., Duprez, D., De Buyzere, M., & Clement, D. L. (1998). How to study sympatho-vagal balance in arterial hypertension and the effect of antihypertensive drugs? Acta Cardiologica, 53, 143–152.PubMed

55.

Kleiger, R. E., Stein, P. K., & Bigger, J. T, Jr. (2005). Heart rate variability: Measurement and clinical utility. Annals of Noninvasive Electrocardiology, 10, 88–101.CrossRefPubMed

56.

Cabral, A. M., & Vasquez, E. C. (1991). Time course of cardiac sympathetic and vagal tone changes in renovascular hypertensive rats. American Journal of Hypertension, 4, 815–819.CrossRefPubMed

57.

Wang, J., Wu, J., & Zhang, Z. (2006). Oxidative stress in mouse brain exposed to lead. The Annals of occupational hygiene, 50(4), 405–409.PubMed

58.

Shin, C. Y., Choi, J. W., Choi, M. S., Ryu, J. R., Ko, K. H., & Cheong, J. H. (2007). Developmental changes of the activity of monoamine oxidase in pre- and postnatally lead exposed rats. Environmental Toxicology and Pharmacology, 24(1), 5–10.CrossRefPubMed

59.

Xu, J., Yan, C. H., Yang, B., Xie, H. F., Zou, X. Y., Zhong, L., et al. (2009). The role of metabotropic glutamate receptor 5 in developmental lead neurotoxicity. Toxicology Letters, 191(2–3), 223–230.CrossRefPubMed

60.

Guimarães, D., Santos, J. P., Carvalho, M. L., Diniz, M. S., House, B., & Miller, V. M. (2014). Analytical evidence of heterogeneous lead accumulation in the hypothalamic defence area and nucleus tractus solitarius. Neurotoxicology, 44, 91–97.CrossRefPubMed

61.

Lin, L. H., Moore, S. A., Jones, S. Y., McGlashon, J., & Talman, W. T. (2013). Astrocytes in the rat nucleus tractus solitarii are critical for cardiovascular reflex control. The Journal of Neuroscience, 33(47), 18608–18617.CrossRefPubMedPubMedCentral

62.

Botelho-Ono, M. S., Pina, H. V., Sousa, K. H., Nunes, F. C., Medeiros, I. A., & Braga, V. A. (2011). Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats. Autonomic Neuroscience, 159(1–2), 38–44.CrossRefPubMed

63.

Prentice, R. C., & Kopp, S. J. (1985). Cardiotoxicity of lead at various perfusate calcium concentrations: Functional and metabolic responses of the perfused rat heart. Toxicology and Applied Pharmacology, 81, 491–501.CrossRefPubMed

64.

Fioresi, M., Furieri, L. B., Simões, M. R., Ribeiro, R. F, Jr., Meira, E. F., Fernandes, A. A., et al. (2013). Acute exposure to lead increases myocardial contractility independent of hypertension development. Brazilian Journal of Medical and Biological Research, 46(2), 178–185.CrossRefPubMedPubMedCentral

65.

Vassallo, D. V., Lebarch, E. C., Moreira, C. M., Wiggers, G. A., & Stefanon, I. (2008). Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium. Brazilian Journal of Medical and Biological Research, 41(9), 789–795.CrossRefPubMed

66.

Monfredi, O., Maltsev, V. A., & Lakatta, E. G. (2013). Modern concepts concerning the origin of the heartbeat. Physiology, 28, 74–92.CrossRefPubMedPubMedCentral

67.

Scott, B., & Lew, J. (1985). Chronic exposure to lead causes persistent alterations in the electric membrane properties of neurons in cell culture. Journal of Neurobiology, 16(6), 425–433.CrossRefPubMed

68.

Szücs, A., Salánki, J., & Rózsa, K. S. (1994). Effects of chronic exposure to cadmium- or lead-enriched environments on ionic currents of identified neurons in Lymnaea stagnalis L. Cellular and Molecular Neurobiology, 14(6), 769–780.CrossRefPubMed

69.

Fiorim, J., Ribeiro, R. F, Jr., Azevedo, B. F., Simões, M. R., Padilha, A. S., Stefanon, I., et al. (2012). Activation of K+ channels and Na+/K+ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats. Toxicology and Applied Pharmacology, 262(1), 22–31.CrossRefPubMed

70.

Kempe, D. S., Lang, P. A., Eisele, K., Klarl, B. A., Wieder, T., Huber, S. M., et al. (2005). Stimulation of erythrocyte phosphatidylserine exposure by lead ions. American Journal of Physiology. Cell Physiology, 288(2), C396–C402.CrossRefPubMed

Titel: Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats
verfasst von: Maylla Ronacher Simões
Silvio César Preti
Bruna Fernandes Azevedo
Jonaína Fiorim
David D. Freire Jr.
Emilia Polaco Covre
Dalton Valentim Vassallo
Leonardo dos Santos
Publikationsdatum: 07.06.2016
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 2/2017
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-016-9374-y

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats

Abstract

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

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