Published Online
on June 13, 2005

A more recent version of this article appeared on July 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/1/107    most recent 01.HYP.0000171479.36880.17v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blanco-Rivero, J. Articles by Balfagón, G. Search for Related Content PubMed PubMed Citation Articles by Blanco-Rivero, J. Articles by Balfagón, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Other hypertension Peripheral vascular disease Endothelium/vascular type/nitric oxide Related Article

Submitted on February 22, 2005
Revised on March 15, 2005

Participation of Prostacyclin in Endothelial Dysfunction Induced by Aldosterone in Normotensive and Hypertensive Rats

Javier Blanco-Rivero; Victoria Cachofeiro; Vicente Lahera; Rosa Aras-Lopez; Iván Márquez-Rodas; Mercedes Salaices; Fabiano E. Xavier; Mercedes Ferrer; and Gloria Balfagón^*

From the Departamentos de Fisiología (J.B.-R., R.A.-L., I.M.-R., M.F., G.B.) y Farmacología (M.S.), Facultad de Medicina, Universidad Autónoma; Departamento de Fisiología (V.C., V.L.), Facultad de Medicina, Universidad Complutense, Madrid, Spain; and Programa de Pós-Graduação em Ciências Fisiológicas/ UFES (F.E.X.), Vitória-ES, Brazil.

^* To whom correspondence should be addressed. E-mail: gloria.balfagon{at}uam.es.

Abstract--The aim of the present study was to analyze the possible involvement of vasoconstrictors prostanoids on the reduced endothelium-dependent relaxations produced by chronic administration of aldosterone in Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). For this purpose, acetylcholine (ACh) relaxations in aortic segments from both strains were analyzed in absence and presence of the cyclooxygenase-1 (COX-1) and COX-2 inhibitor indomethacin, the specific COX-2 inhibitor NS-398, the TP receptor antagonist (SQ 29 548), the thromboxane A₂ (TXA₂) synthase inhibitor furegrelate, and the prostacyclin (PGI₂) synthesis inhibitor tranylcypromine (TCP). In addition, COX-2 protein expression was studied by Western blot analysis. Release of prostaglandin E₂ (PGE₂) and the metabolites of PGF₂, TXA₂, and PGI₂, 13,14-dihydro-15-keto PGF_2a, TXB₂, and 6-keto-PGF₁, respectively, were measured. Treatment with aldosterone did not modify blood pressure levels in any strain. However, aldosterone markedly reduced (P<0.05) ACh-induced relaxations in segments from both strains in a similar extent. Indomethacin, NS-398, SQ 29 548, and TCP enhanced (P<0.05) ACh relaxations in both strains treated with aldosterone. Aortic COX-2 protein expression was higher in both strains of rats treated with aldosterone. In normotensive animals, aldosterone increases the ACh-stimulated aortic production of 13,14-dihydro-15-keto PGF_2a, PGE₂, and 6-keto-PGF₁ (P<0.05). In SHR, ACh only increased the 6-keto-PGF₁ production (P<0.05). It could be concluded that chronic treatment with aldosterone was able to produce endothelial dysfunction through COX-2 activation in normotensive and hypertensive conditions. PGI₂ seems to be the main factor accounting for endothelial dysfunction in hypertensive rats, whereas other prostanoids besides PGI₂ appear to be involved in endothelial dysfunction under normotensive conditions.

Key words: aldosterone • endothelium • prostacyclin • normotension • hypertension

Related Article:

Aldosterone Promotes Endothelial Dysfunction Via Prostacyclin Independent of Hypertension

Fruzsina K. Johnson, Robert A. Johnson, and William Durante
Hypertension 2005 46: 29-30. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				A. Martorell, A. Sagredo, R. Aras-Lopez, G. Balfagon, and M. Ferrer Ovariectomy increases the formation of prostanoids and modulates their role in acetylcholine-induced relaxation and nitric oxide release in the rat aorta Cardiovasc Res, November 1, 2009; 84(2): 300 - 308. [Abstract] [Full Text] [PDF]

				A. Tasatargil, M. Tekcan, C. Celik-Ozenci, N. Ece Gungor, and B. Dalkiran Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation Journal of Renin-Angiotensin-Aldosterone System, September 1, 2009; 10(3): 127 - 137. [Abstract] [PDF]

				Z. A. Radi Pathophysiology of Cyclooxygenase Inhibition in Animal Models Toxicol Pathol, January 1, 2009; 37(1): 34 - 46. [Abstract] [Full Text] [PDF]

				P. M. Vanhoutte and E. H. C. Tang Endothelium-dependent contractions: when a good guy turns bad! J. Physiol., November 15, 2008; 586(22): 5295 - 5304. [Abstract] [Full Text] [PDF]

				G. Lastra, A. Whaley-Connell, C. Manrique, J. Habibi, A. A. Gutweiler, L. Appesh, M. R. Hayden, Y. Wei, C. Ferrario, and J. R. Sowers Low-dose spironolactone reduces reactive oxygen species generation and improves insulin-stimulated glucose transport in skeletal muscle in the TG(mRen2)27 rat Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E110 - E116. [Abstract] [Full Text] [PDF]

				L del Campo, A Sagredo, R Aras-Lopez, G Balfagon, and M Ferrer Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery J. Endocrinol., May 1, 2008; 197(2): 371 - 379. [Abstract] [Full Text] [PDF]

				T. Imanishi, H. Ikejima, H. Tsujioka, A. Kuroi, K. Kobayashi, Y. Muragaki, S. Mochizuki, M. Goto, K. Yoshida, and T. Akasaka Addition of Eplerenone to an Angiotensin-Converting Enzyme Inhibitor Effectively Improves Nitric Oxide Bioavailability Hypertension, March 1, 2008; 51(3): 734 - 741. [Abstract] [Full Text] [PDF]

				A. Martorell, J. Blanco-Rivero, R. Aras-Lopez, A. Sagredo, G. Balfagon, and M. Ferrer Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta Cardiovasc Res, February 1, 2008; 77(3): 590 - 599. [Abstract] [Full Text] [PDF]

				M.-L. Ambroisine, J. Favre, P. Oliviero, C. Rodriguez, J. Gao, C. Thuillez, J.-L. Samuel, V. Richard, and C. Delcayre Aldosterone-Induced Coronary Dysfunction in Transgenic Mice Involves the Calcium-Activated Potassium (BKCa) Channels of Vascular Smooth Muscle Cells Circulation, November 20, 2007; 116(21): 2435 - 2443. [Abstract] [Full Text] [PDF]

				S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF]

				J. Blanco-Rivero, I. Marquez-Rodas, F. E. Xavier, R. Aras-Lopez, I. Arroyo-Villa, M. Ferrer, and G. Balfagon Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway Cardiovasc Res, July 15, 2007; 75(2): 398 - 407. [Abstract] [Full Text] [PDF]

				E. L. Schiffrin Effects of Aldosterone on the Vasculature Hypertension, March 1, 2006; 47(3): 312 - 318. [Full Text] [PDF]

				M. Hermann, H. Krum, and F. Ruschitzka To the Heart of the Matter: Coxibs, Smoking, and Cardiovascular Risk Circulation, August 16, 2005; 112(7): 941 - 945. [Full Text] [PDF]

				F. K. Johnson, R. A. Johnson, and W. Durante Aldosterone Promotes Endothelial Dysfunction Via Prostacyclin Independent of Hypertension Hypertension, July 1, 2005; 46(1): 29 - 30. [Full Text] [PDF]