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.