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(Hypertension. 2005;46:107.)
© 2005 American Heart Association, Inc.

Original Articles

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; 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.

Correspondence to G. Balfagón, Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain. E-mail gloria.balfagon{at}uam.es

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

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Aldosterone Promotes Endothelial Dysfunction Via Prostacyclin Independent of Hypertension

Fruzsina K. Johnson, Robert A. Johnson, and William Durante
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