This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Tasatargil, A. Articles by Dalkiran, B. PubMed PubMed Citation Articles by Tasatargil, A. Articles by Dalkiran, B. Social Bookmarking                         What's this?

Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation

Department of Pharmacology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey, ardatas{at}akdeniz.edu.tr

Merih Tekcan

Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey

Ciler Celik-Ozenci

Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey

Nazli Ece Gungor

Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey

Bedriniam Dalkiran

Department of Pharmacology, Medical Faculty, Akdeniz University, 07070, Antalya, Turkey

Introduction. The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could prevent endothelial dysfunction caused by aldosterone.

Methods. Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry.

Results. There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels.

Conclusion. Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration.

Key Words: aldosterone • aorta • endothelial dysfunction • PARP

References

• Giebisch G. Renal potassium transport: mechanisms and regulation. Am J Physiol 1998;274:F817-33.[Web of Science][Medline] [Order article via Infotrieve]
• Giebisch G., Wang W. Renal tubule potassium channels: function, regulation and structure. Acta Physiol Scand 2000;170:153-73.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Palmer LG Potassium secretion and the regulation of distal nephron K channels. Am J Physiol 1999;277:F821-5.[Web of Science][Medline] [Order article via Infotrieve]
• Palmer LG, Frindt G. Aldosterone and potassium secretion by the cortical collecting duct. Kidney Int 2000;57:1324-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Schiffrin EL Effects of aldosterone on the vasculature. Hypertension 2006;47:312-18.[Free Full Text]
• Takeda Y., Yoneda T., Demura M., Miyamori I., Mabuchi H. Cardiac aldosterone production in genetically hypertensive rats. Hypertension 2000;36:495-500.[Abstract/Free Full Text]
• Funder JW Mineralocorticoid receptors and cardiovascular damage: it’s not just aldosterone. Hypertension 2006;47:634-5.[Free Full Text]
• Hashikabe Y., Suzuki K., Jojima T., Uchida K., Hattori Y. Aldosterone impairs vascular endothelial cell function. J Cardiovasc Pharmacol 2006;47:609-13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Safar ME Systolic hypertension in the elderly: arterial wall mechanical properties and the renin-angiotensin-aldosterone system. J Hypertens 2005;23:673-81.[Web of Science][Medline] [Order article via Infotrieve]
• Cachofeiro V., Miana M., de Las Heras N. et al. Aldosterone and the vascular system. J Steroid Biochem Mol Biol 2008;109:331-5.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Oberleithner H., Ludwig T., Riethmuller C. et al. Human endothelium: target for aldosterone. Hypertension 2004; 43:952-6.[Abstract/Free Full Text]
• Skøtt O., Uhrenholt TR, Schjerniog J., Hansen PBL, Rasmussen LE, Jensen BL Rapid actions of aldosterone in vascular health and disease - friend or foe? Pharmacol Ther 2006;2:495-507.
• Golestaneh N., Klein C., Valamanesh F., Suarez G., Agarwal MK, Mirshahi M. Mineralocorticoid receptor-mediated signaling regulates the ion gated sodium channel in vascular endothelial cells and requires an intact cytoskeleton. Biochem Biophys Res Commun 2001;80:1300-06.
• Oberleithner H., Riethmuller C., Ludwig T. et al. Differential action of steroid hormones on human endothelium. J Cell Sci 2006;119:1926-32.[Abstract/Free Full Text]
• Oberleithner H. Is the vascular endothelium under the control of aldosterone? Facts and hypothesis. Pflugers Arch Eur J Physiol 2007;454:187-93.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Dworakowski R., Alom-Ruiz SP, Shah AM NADPH oxidase-derived reactive oxygen species in the regulation of endothelial phenotype. Pharmacol Rep 2008;60:21-3.[Web of Science][Medline] [Order article via Infotrieve]
• Farquharson CA, Struthers AD Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci 2002;103:425-31.[Web of Science][Medline] [Order article via Infotrieve]
• Virdis A., Neves MF, Amir F., Viel E., Touyz RM, Schiffrin EL Spironolactone improves angiotensin-induced vascular changes and oxidative stress. Hypertension 2002;40:504-10.[Abstract/Free Full Text]
• Blanco-Rivero J., Cachofeiro V., Lahera V. et al. Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats. Hypertension 2005;46:107-12.[Abstract/Free Full Text]
• Freel EM, Connell JM Mechanisms of hypertension: the expanding role of aldosterone. J Am Soc Nephrol 2004;15:1993-2001.[Abstract/Free Full Text]
• Funder JW Non-genomic actions of aldosterone: role in hypertension. Curr Opin Nephrol Hypertens 2001;10:227-30.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Münzel T., Just H., Harrison DG The physiology and pathophysiology of the nitric oxide/superoxide system. In: Born GVR and Schwartz CJ (eds.). Vascular Endothelium: Physiology, Pathology and Therapeutic Options. Stuttgart: Schattauer, 1997;205-20.
• Radovits T., Lin LN, Zotkina J. et al. Poly(ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by reactive oxidant hydrogen peroxide in vitro. Eur J Pharmacol 2007;564:158-66.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Berger NA Poly (ADP-ribose) in the cellular response to DNA damage. Radic Res 1985;101:4-15.[CrossRef]
• Pacher P., Liaudet L., Bai P. et al. Activation of poly (ADP-ribose) polymerase contributes to development of doxorubicininduced heart failure. J Pharmacol Exp Ther 2002;300:862-7.[Abstract/Free Full Text]
• Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG DNA strand breaks activate poly adenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986;77:1312-20.[Web of Science][Medline] [Order article via Infotrieve]
• Eliasson MJ, Sampei K., Mandir AS et al. Poly (ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 1997;3:1089-95.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Liaudet L., Soriano FG, Szabo E. et al. Protection against hemorrhagic shock in mice genetically deficient in poly (ADP-ribose) polymerase. Proc Natl Acad Sci U S A 2000;97:10203-08.[Abstract/Free Full Text]
• Pacher P., Mabley JG, Soriano FG, Liaudet L., Komjati K., Szabo C. Endothelial dysfunction in aging animals: the role of poly (ADP-ribose) polymerase activation. Br J Pharmacol 2002;135:1347-50.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pacher P., Liaudet L., Soriano FG, Mabley JG, Szabo E., Szabo C. The role of poly (ADP-ribose) polymerase in the development of cardiovascular dysfunction in diabetes mellitus. Diabetes 2002;51:514-21.[Abstract/Free Full Text]
• Tasatargil A., Dalaklioglu S., Sadan G. Poly (ADP-ribose) polymerase inhibition prevents homocysteine-induced endothelial dysfunction in isolated rat aorta. Pharmacology 2004;72:99-105.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Tasatargil A., Dalaklioglu S., Sadan G. Inhibition of poly(ADP-ribose) polymerase prevents vascular hyporesponsiveness induced by lipopolysaccharide in isolated rat aorta. Pharmacol Res 2005;51:581-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Tasatargil A., Aksoy NH, Dalaklioglu S., Sadan G. Poly (ADP-ribose) polymerase as a potential target for the treatment of acute renal injury caused by lipopolysaccharide. Ren Fail 2008;30:115-20.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Zingarelli B., Salzman AL, Szabo C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intracellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 1998;83:85-94.[Abstract/Free Full Text]
• Duprez D., De Buyzere M., Rietzschel ER, Clement DL Aldosterone and vascular damage. Curr Hypertens Rep 2000;2:327-34.[Medline] [Order article via Infotrieve]
• Nishizaka MK, Zaman MA, Green SA, Renfroe KY, Calhoun DA Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 2004;109:2857-61.[Abstract/Free Full Text]
• Pu Q., Neves MF, Virdis A., Touyz RM, Schiffrin EL Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension 2003; 42:49-55.[Abstract/Free Full Text]
• Ahokas RA, Warrington KJ, Gerling IC et al. Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circ Res 2003;93:e124-35.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Iglarz M., Touyz RM, Viel EC, Amiri F., Schiffrin EL Involvement of oxidative stress in the profibrotic action of aldosterone interaction with the renin-angiotensin system. Am J Hypertens 2004;17:597-603.[Web of Science][Medline] [Order article via Infotrieve]
• Virag L., Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 2002;54:375-429.[Abstract/Free Full Text]
• Garcia Soriano F., Virag L., Jagtap P. et al. Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 2001;7:108-13.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pieper AA, Walles T., Wei G. et al. Myocardial postischemic injury is reduced by poly (ADP-ribose) polymerase-1 gene disruption. Mol Med 2000;6:271-82.[Web of Science][Medline] [Order article via Infotrieve]
• Yamamoto M., Hara H., Adachi T. Effects of homocysteine on the binding of extracellular-superoxide dismutase to the endothelial cell surface. FEBS Lett 2000;486:159-62.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Szabo C., Cuzzocrea S., Zingarelli B., O’Connor M., Salzman AL Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 1997;100:723-35.[Web of Science][Medline] [Order article via Infotrieve]
• Soriano FG, Virag L., Szabo C. Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. J Mol Med 2001;79:437-48.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 10, No. 3, 127-137 (2009)
DOI: 10.1177/1470320309343655


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Tasatargil, A. Articles by Dalkiran, B. PubMed PubMed Citation Articles by Tasatargil, A. Articles by Dalkiran, B. Social Bookmarking                         What's this?