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 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␣ , TXA 2 , and PGI 2 , 13,14-dihydro-15-keto PGF 2a , TXB 2 , and 6-keto-PGF 1␣ , respectively, were measured. Treatment with aldosterone did not modify blood pressure levels in any strain. However, aldosterone markedly reduced (PϽ0.05) ACh-induced relaxations in segments from both strains in a similar extent. Indomethacin, NS-398, SQ 29 548, and TCP enhanced (PϽ0.05) 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␣ (PϽ0.05). In SHR, ACh only increased the 6-keto-PGF 1␣ production (PϽ0.05). 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. Key Words: aldosterone Ⅲ endothelium Ⅲ prostacyclin Ⅲ normotension Ⅲ hypertension A ldosterone is a mineralocorticoid that participates in electrolyte balance and plays an important physiological role in the long-term regulation of Na ϩ and K ϩ in the distal tubule and collecting duct. [1][2][3][4] To date, several studies suggested that aldosterone plays a larger role than once appreciated in the regulation of vascular tone as well as in cardiovascular alterations such as endothelial dysfunction, vascular fibrosis, and inflammation, left ventricular hypertrophy, congestive heart failure, and cardiac arrhythmias. [5][6][7][8][9][10][11][12] Furthermore, aldosterone has also been shown to be involved in the pathogenesis of hypertension. [13][14][15] In general terms, endothelial dysfunction is characterized by reduced endothelium-dependent relaxations, suggesting a reduced availability of NO attributable to a reduction of NO production or enhanced NO inactivation. 16,17 In addition, an increased production of vasoconstrictor factors could be also responsible for the reduced endothelium-dependent...