AT2 receptors contribute to acute blood pressure-lowering and vasodilator effects of AT1 receptor antagonism in conscious normotensive but not hypertensive rats

The aims of this study were to determine the contribution of the AT(2) receptor to the antihypertensive and regional vasodilatory effects of AT(1) receptor blockade in adult spontaneously hypertensive rats ( SHR), 2-kidney, 1-clip hypertensive (2K1C) rats, and sham-operated normotensive rats. Several studies have provided evidence to support the notion that the AT(2) receptor may have opposing effects to those mediated by the AT(1) receptor. We therefore tested the hypothesis that the depressor and vasodilator effects of acute AT(1) receptor blockade are dependent on AT(2) receptor activation. Heart rate, mean arterial pressure, and regional hemodynamics were measured over a 4-day protocol in rats that received the following treatments in randomized order: saline vehicle, the AT(1) receptor antagonist candesartan (0.1 mg/kg iv bolus), the AT(2) receptor antagonist PD-123319 (50 mu g circle kg(-1)circle min(-1)), or both antagonists. Intravenous candesartan reduced mean arterial pressure in all groups of rats, and this was accompanied by renal and mesenteric vasodilation. Neither saline nor PD-123319 significantly affected these variables. Concomitant PD123319 administration partially reversed the depressor and mesenteric vasodilator effects of candesartan in sham-operated normotensive rats but not in SHR or 2K1C rats. These data indicate that the AT(2) receptor contributes to the blood pressure-lowering and mesenteric vasodilator effects of AT(1) receptor blockade in the acute setting in conscious normotensive but not hypertensive rats.