Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats

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 A(2) ( TXA(2)) synthase inhibitor furegrelate, and the prostacyclin ( PGI(2)) synthesis inhibitor tranylcypromine ( TCP). In addition, COX-2 protein expression was studied by Western blot analysis. Release of prostaglandin E-2 ( PGE(2)) and the metabolites of PGF(2 alpha), TXA(2), and PGI(2), 13,14-dihydro-15-keto PGF(2a), TXB2, and 6-keto-PGF(1 alpha), 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), PGE(2), and 6-keto-PGF(1 alpha) ( P < 0.05). In SHR, ACh only increased the 6-keto-PGF(1 alpha) 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. PGI(2) seems to be the main factor accounting for endothelial dysfunction in hypertensive rats, whereas other prostanoids besides PGI(2) appear to be involved in endothelial dysfunction under normotensive conditions.