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

• Published in: Journal of cardiovascular pharmacology Vol. 36; no. 5 Suppl 1; p. S99
• Main Authors: Tostes, R C, David, F L, Carvalho, M H, Nigro, D, Scivoletto, R, Fortes, Z B
• Format: Journal Article
• Language: English
• Published: United States 2000
• Subjects: Animals; Desoxycorticosterone - pharmacology; Endothelin-1 - pharmacology; Endothelins - pharmacology; Female; Hypertension - physiopathology; In Vitro Techniques; Male; Peptide Fragments - pharmacology; Rats; Rats, Wistar; Sex Characteristics; Sodium Chloride - pharmacology; Vasoconstriction - drug effects
• ISSN: 0160-2446
• DOI: 10.1097/00005344-200036001-00032

In experimental models of hypertension, blood pressure reaches a higher level in male than in female rats. Because endothelin-1 (ET-1) seems to play a role in blood pressure elevation in deoxycorticosterone acetate (DOCA)-salt hypertension, we hypothesized that male DOCA-salt rats would display a greater 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 and tap water. Responses to ET-1, norepinephrine (NE), serotonin (5-HT), IRL-1620, a selective endothelin-B- (ET(B)) receptor agonist, and acetylcholine (ACh) were evaluated in isolated aortic rings and also in vivo in the mesenteric microcirculation. Endothelium-intact aortas from male and female DOCA rats displayed increased sensitivity (p < 0.05) to NE and 5-HT, but decreased 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, but no changes in ET-1 sensitivity were observed in female DOCA aortas. IRL-1620 induced contraction in male DOCA aortas, but not in female DOCA or control endothelium-denuded aortas. In the microcirculation, IRL-1620 induced vasodilation in male and female control rats, but marked vasoconstriction in male DOCA and minimal changes in vessels diameter in female DOCA rats. Bosentan, an ET(A)/ET(B)-receptor antagonist, induced a greater decrease in mean arterial blood pressure in male than in female DOCA-salt hypertensive rats. These data support the hypothesis that DOCA-salt rats exhibit gender differences in ET-1 vascular reactivity, which probably result from functional changes in ET(B)-receptors. The increased ET(B) responses in male DOCA-salt hypertensive rats may play a role in their higher blood pressure levels.