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2012 | 7 | 6 | 704-712

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New evidence for vascular interactions between aldosterone, angiotensin II and antioxidants in isolated smooth muscle cells of rats


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Accumulating evidence suggests that the nongenomic cardiovascular actions of aldosterone are produced by varied cellular pathways and mediated by a multitude of messenger systems including the reactive oxygen and nitrogen species. Considering the involvement of the oxidative and nitrosative stress in the pathways leading to the activation of the angiotensin - aldosterone system, in the current study we tried to evaluate the functional interactions between aldosterone, angiotensin II and antioxidants in isolated vascular smooth muscle of aortic rings from rats. Our data provide additional arguments that the nongenomic actions of aldosterone on aortic smooth muscle cells of rats are a question of cross-talk and balance between its rapid vasoconstrictor and vasodilator effects, as result of the activation of reactive oxygen species in the first case and of nitrogen species in the second. In this way, it seems that at low ambient oxidative stress, aldosterone promotes nitric oxide (NO) production and vasodilatation, while in situations with increased oxidative stress the endothelial dysfunction and detrimental effects induced by vasoconstriction will prevail. Thus, aldosterone could be considered both “friend and foe”. This could be relevant for the ways in which aldosterone damages cardiovascular functions and could lead to significant therapeutic improvements.










Physical description


1 - 12 - 2012
11 - 10 - 2012


  • “Gr. T. Popa” University of Medicine and Pharmacy, Str. Universitatii, Nr. 16, Iasi, 700115, Romania


  • [1] Connell JM, Davies E. The new biology of aldosterone. J Endocrinol. 2005 Jul;186(1):1–20 http://dx.doi.org/10.1677/joe.1.06017[Crossref]
  • [2] Spieker LE, Flammer AJ, Luscher TF. The vascular endothelium in hypertension. Handb Exp Pharmacol. 2006 (176 Pt 2):249–283
  • [3] Christy C, Hadoke PW, Paterson JM, Mullins JJ, Seckl JR, Walker BR. 11beta-hydroxysteroid dehydrogenase type 2 in mouse aorta: localization and influence on response to glucocorticoids. Hypertension. 2003 Oct;42(4):580–587 http://dx.doi.org/10.1161/01.HYP.0000088855.06598.5B[Crossref]
  • [4] Losel R, Schultz A, Boldyreff B, Wehling M. Rapid effects of aldosterone on vascular cells: clinical implications. Steroids. 2004 Aug;69(8–9):575–578 http://dx.doi.org/10.1016/j.steroids.2004.05.005[Crossref]
  • [5] Chai W, Garrelds IM, de Vries R, Batenburg WW, van Kats JP, Danser AH. Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. Hypertension. 2005 Oct;46(4):701–706 http://dx.doi.org/10.1161/01.HYP.0000182661.98259.4f[Crossref]
  • [6] Jennings DL, Kalus JS, O’Dell KM. Aldosterone receptor antagonism in heart failure. Pharmacotherapy. 2005 Aug;25(8):1126–1133 http://dx.doi.org/10.1592/phco.2005.25.8.1126[Crossref]
  • [7] Ciobica A, Bild W, Hritcu L, Haulica I. Brain reninangiotensin system in cognitive function: preclinical findings and implications for prevention and treatment of dementia. Acta Neurol Belg. 2009 Sep;109(3):171–180
  • [8] Min LJ, Mogi M, Li JM, Iwanami J, Iwai M, Horiuchi M. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ Res. 2005 Sep 2;97(5):434–442 http://dx.doi.org/10.1161/01.RES.0000180753.63183.95[Crossref]
  • [9] Hashikabe Y, Suzuki K, Jojima T, Uchida K, Hattori Y. Aldosterone impairs vascular endothelial cell function. J Cardiovasc Pharmacol. 2006 Apr;47(4):609–613 http://dx.doi.org/10.1097/01.fjc.0000211738.63207.c3[Crossref]
  • [10] Schmidt BM, Oehmer S, Delles C, Bratke R, Schneider MP, Klingbeil A, et al. Rapid nongenomic effects of aldosterone on human forearm vasculature. Hypertension. 2003 Aug;42(2):156–160 http://dx.doi.org/10.1161/01.HYP.0000083298.23119.16[Crossref]
  • [11] Miyata K, Rahman M, Shokoji T, Nagai Y, Zhang GX, Sun GP, et al. Aldosterone stimulates reactive oxygen species production through activation of NADPH oxidase in rat mesangial cells. J Am Soc Nephrol. 2005 Oct;16(10):2906–2912 http://dx.doi.org/10.1681/ASN.2005040390[Crossref]
  • [12] Bild W, Ciobica A, Padurariu M, Bild V. The interdependence of the reactive species of oxygen, nitrogen, and carbon. J Physiol Biochem. 2012 Mar 29 [WoS]
  • [13] Skott O, Uhrenholt TR, Schjerning J, Hansen PB, Rasmussen LE, Jensen BL. Rapid actions of aldosterone in vascular health and disease-friend or foe? Pharmacol Ther. 2006 Aug;111(2):495–507 http://dx.doi.org/10.1016/j.pharmthera.2005.10.010[Crossref]
  • [14] Ciobica Alin, Hritcu L, Veronica Nastasa, Manuela Padurariu, Walther Bild. Inhibition of central angiotensin converting enzyme exerts anxiolytic effects by decreasing brain oxidative stress. J Med Biochem. 2011;30:109–114 http://dx.doi.org/10.2478/v10011-011-0009-3[Crossref][WoS]
  • [15] Ciobica Alin, Veronica Bild, Lucian Hritcu, Manuela Padurariu, Walther Bild. Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat. Central European Journal of Medicine. 2011;6:331–340 http://dx.doi.org/10.2478/s11536-011-0010-8[WoS][Crossref]
  • [16] Ciobica A, Bild W, Hritcu L, Artenie V, Haulica I. The importance of oxidative stress in angiotensin II-mediated effects on cognitive functions. Neuropeptides 2009;43:420–421
  • [17] Wilson SK. Role of oxygen-derived free radicals in acute angiotensin II-induced hypertensive vascular disease in the rat. Circ Res. 1990 Mar;66(3):722–734 http://dx.doi.org/10.1161/01.RES.66.3.722[Crossref]
  • [18] Millatt LJ, Abdel-Rahman EM, Siragy HM. Angiotensin II and nitric oxide: a question of balance. Regul Pept. 1999 May 31;81(1–3):1–10 http://dx.doi.org/10.1016/S0167-0115(99)00027-0[Crossref]
  • [19] Haulica I, Todiras M, Brailoiu E, Baltatu O. Modulatory role of nitric oxide on angiotensins vasoconstriction. Rom J Physiol. 1996 Jan–Dec;33(1–4):83–90
  • [20] Usui M, Egashira K, Kitamoto S, Koyanagi M, Katoh M, Kataoka C, et al. Pathogenic role of oxidative stress in vascular angiotensin-converting enzyme activation in long-term blockade of nitric oxide synthesis in rats. Hypertension. 1999 Oct;34(4 Pt 1):546–551 http://dx.doi.org/10.1161/01.HYP.34.4.546[Crossref]
  • [21] Kazama K, Anrather J, Zhou P, Girouard H, Frys K, Milner TA, et al. Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals. Circ Res. 2004 Nov 12;95(10):1019–1026 http://dx.doi.org/10.1161/01.RES.0000148637.85595.c5[Crossref]
  • [22] Ramires FJ, Mansur A, Coelho O, Maranhao M, Gruppi CJ, Mady C, et al. Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol. 2000 May 15;85(10):1207–1211 http://dx.doi.org/10.1016/S0002-9149(00)00729-3[Crossref]
  • [23] Zhao W, Ahokas RA, Weber KT, Sun Y. ANG IIinduced cardiac molecular and cellular events: role of aldosterone. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H336–343 http://dx.doi.org/10.1152/ajpheart.01307.2005[Crossref]
  • [24] Williams TA, Verhovez A, Milan A, Veglio F, Mulatero P. Protective effect of spironolactone on endothelial cell apoptosis. Endocrinology. 2006 May;147(5):2496–2505 http://dx.doi.org/10.1210/en.2005-1318[Crossref]
  • [25] Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure. J Nucl Med. 2002 Oct;43(10):1279–1285 [WoS]
  • [26] Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309–1321 http://dx.doi.org/10.1056/NEJMoa030207[Crossref]
  • [27] Michea L, Delpiano AM, Hitschfeld C, Lobos L, Lavandero S, Marusic ET. Eplerenone blocks nongenomic effects of aldosterone on the Na+/ H+ exchanger, intracellular Ca2+ levels, and vasoconstriction in mesenteric resistance vessels. Endocrinology. 2005 Mar;146(3):973–980 http://dx.doi.org/10.1210/en.2004-1130[Crossref]
  • [28] Yamanari H, Nakamura K, Miura D, Yamanari S, Ohe T. Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress. Clin Exp Hypertens. 2009 Oct;31(7):585–594 http://dx.doi.org/10.3109/10641960902929438[Crossref]
  • [29] Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142
  • [30] Lazartigues E, Lawrence AJ, Lamb FS, Davisson RL. Renovascular hypertension in mice with brainselective overexpression of AT1a receptors is buffered by increased nitric oxide production in the periphery. Circ Res. 2004 Sep 3;95(5):523–531 http://dx.doi.org/10.1161/01.RES.0000140892.86313.c2[Crossref]
  • [31] Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda). 2006 Aug;21:269–280 http://dx.doi.org/10.1152/physiol.00004.2006[Crossref]
  • [32] Santini V, Giles FJ. The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035–1042.
  • [33] Aitio ML. N-acetylcysteine - passe-partout or much ado about nothing? Br J Clin Pharmacol. 2006 Jan;61(1):5–15 http://dx.doi.org/10.1111/j.1365-2125.2005.02523.x[Crossref]
  • [34] Whaley-Connell A, Sowers JR. Oxidative Stress in the Cardiorenal Metabolic Syndrome Curr Hypertens Rep. 2012 May 13
  • [35] Aroor AR, Mandavia C, Ren J, Sowers JR, Pulakat L. Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome Cardiorenal Med. 2012 May;2(2):87–109
  • [36] Chu PY, Zatta A, Kiriazis H, Chin-Dusting J, Du XJ, Marshall T, Kaye DM. CXCR4 antagonism attenuates the cardiorenal consequences of mineralocorticoid excess. Circ Heart Fail. 2011 Sep;4(5):651–658 http://dx.doi.org/10.1161/CIRCHEARTFAILURE.110.960831[WoS]

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