Gender differences in vascular reactivity to endothelin-1 in deoxycorticosterone-salt hypertensive rats

In experimental models of hypertension, blood pressure reaches a higher lev el in male than in female rats. Because endothelin-1 (ET-1) seems to play a role in blood pressure elevation in deoxycorticosterone acetate (DOCA)-sal t hypertension, we hypothesized that male DOCA-salt rats would display a gr eater vascular responsiveness to ET-1 than female DOCA-salt rats. Male and female Wistar rats were uninephrectomized, received DOCA injections (50 mg/ kg/week) and water plus 1.0% NaCl/0.2% KCl. Control rats received vehicle a nd tap water. Responses to ET-1, norepinephrine (NE), serotonin (5-HT), IRL -1620, a selective endothelin-B- (ETB) receptor agonist, and acetylcholine (ACh) were evaluated in isolated aortic rings and also in vivo in the mesen teric microcirculation. Endothelium-intact aortas from male and female DOCA rats displayed increased sensitivity (p < 0.05) to NE and 5-HT, but decrea sed relaxation to ACh in comparison to aortas from respective control male and female rats. Endothelium-denuded, but not endothelium-intact, arteries from male DOCA rats displayed increased sensitivity (-log EC20) to ET-1, bu t no changes in ET-1 sensitivity were observed in female DOCA aortas. IRL-1 620 induced contraction in male DOCA aortas, but not in female DOCA or cont rol endothelium-denuded aortas. In the microcirculation, IRL-1620 induced v asodilation in male and female control rats, but marked vasoconstriction in male DOCA and minimal changes in vessels diameter in female DOCA rats. Bos entan, an ETA/ETB-receptor antagonist, induced a greater decrease in mean a rterial blood pressure in male than in female DOCA-salt hypertensive rats. These data support the hypothesis that DOCA-salt rats exhibit gender differ ences in ET-1 vascular reactivity, which probably result from functional ch anges in ETB-receptors. The increased ETB responses in male DOCA-salt hyper tensive rats may play a role in their higher blood pressure levels.