High blood pressure reduction reverses angiotensin II type 2 receptor-mediated vasoconstriction into vasodilation in spontaneously hypertensive rats.

Open Access
Publisher Website
Google Scholar
Abstract
Background— We have previously shown that angiotensin II type 2 receptor (AT 2 R) stimulation causes endothelium-dependent vasodilation that does not desensitize after chronic angiotensin II type 1 receptor (AT 1 R) blockade, suggesting a role for AT 2 R in antihypertensive treatment. Methods and Results— We recorded mean arterial pressure (MAP) and investigated AT 2 R by Western blot analysis, immunohistochemistry, and function in isolated mesenteric resistance arteries (205 μm in diameter) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) receiving the following for 4 weeks in drinking water: placebo, AT 1 R blockade (candesartan; 2 mg/kg per day), ACE inhibitor (perindopril; 3 mg/kg per day), nonselective vasodilator (hydralazine; 16 or 24 mg/kg per day), or candesartan plus hydralazine (16 mg/kg per day). In precontracted isolated arteries, AT 2 R stimulation (angiotensin II in the presence of candesartan) caused vasodilation in WKY rats (MAP=118 mm Hg) and vasoconstriction in SHR (MAP=183 mm Hg). In SHR treated with candesartan (MAP=146 mm Hg) or hydralazine (16 mg/kg per day; MAP=145 mm Hg), AT 2 R-induced contraction was reduced by 50%. In SHR treated with perindopril (MAP=125 mm Hg), AT 2 R stimulation induced vasodilation. In SHR treated with hydralazine (24 mg/kg per day; MAP=105 mm Hg) and in SHR treated with hydralazine (16 mg/kg per day) plus candesartan (MAP=102 mm Hg), an AT 2 R-mediated vasodilation was restored. Immunochemistry and Western blot analysis showed that AT 2 R expression, lower in SHR than in WKY rats, was restored to normal levels by treatments reducing arterial pressure in SHR. Conclusions— Our results suggest that in resistance arteries of SHR, (1) AT 2 R is downregulated by hypertension, and (2) specific and nonspecific antihypertensive treatments restore AT 2 R expression and vasodilator functions.

This publication has 30 references indexed in Scilit: