Deoxycorticosterone acetate-salt hypertensive rats display gender-related differences in ETB receptor-mediated vascular responses

1 Male DOCA-salt rats exhibit vasoconstriction upon ETB activation. Because hypertension is less severe in female than male DOCA rats, we hypothesized that female DOCA rats would display attenuated ETB vasoconstrictor respons es. 2 Uninephrectomized Wistar rats received DOCA and drinking water containing NaCl/KCl, Control rats received vehicle and tap water. Systolic blood pres sure was higher in male vs female DOCA rats. Responses to endothelin-1 (ET- 1), IRL-1620, an ETB agonist, and acetylcholine were evaluated in isolated aortas and in vivo in the mesenteric microcirculation. 3 Endothelium-denuded aortas from male, but not female. DOCA rats displayed increased sensitivity to ET-1. IRL-1620 contracted aortas from male DOCA r ats, but not control or female DOCA aortas. Noradrenaline-constricted and e ndothelium-intact aortas from male, but not female, DOCA rats displayed inc reased relaxation to IRL-1620 compared to control aortas. 4 In vivo, increased vasoconstriction to ET-1 was observed in male and fema le DOCA rats. IRL-1620 induced vasodilation in control rats, but vasoconstr iction in male DOCA rats. There were minimal changes in diameter in vessels from female DOCA rats. 5 The initial fall in blood pressure induced by ET-1 and IRL-1620 was atten uated in male DOCA rats. Bosentan, a mixed ETA/ETB, receptor antagonist, lo wered blood pressure in male and female DOCA rats, but a greater and marked decrease occurred in the male DOCA group. 6 The gender-related differences in ET-1/ETB-mediated effects both in the v asculature and blood pressure suggest that sex-related functional up-regula tion of ETB receptors may play a role in the more severe hypertension in ma le DOCA hypertensive rats.