Rca. Tostes et al., Gender differences in vascular reactivity to endothelin-1 in deoxycorticosterone-salt hypertensive rats, J CARDIO PH, 36, 2000, pp. S99-S101
Citations number
14
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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.