Angiotensin Type 2 Receptor-Mediated Hypotension in Angiotensin Type-1 Receptor-Blocked Rats

Abstract

The type-2 (AT ₂ ) angiotensin (Ang) II receptor has been characterized as potentially counterregulatory to the actions of Ang II at its type-1 (AT ₁ ) receptor. We investigated the effects of Ang II and CGP-42112A (CGP), a selective peptide AT ₂ receptor agonist, on blood pressure (BP) in rats with or without pharmacological blockade of the AT ₁ receptor with losartan (LOS) or valsartan (VAL). In anesthetized rats (n=5 per group) receiving normal sodium intake, Ang II (200 pmol/kg per minute IV) alone increased BP from a control of 112±3 to 168±7 mm Hg ( P P P 2 receptor antagonist PD 123,319 (PD) completely blocked the hypotensive response to LOS combined with Ang II ( P =NS from control). In conscious rats (n=5 per group) receiving normal sodium intake, VAL (10 mg/kg) alone decreased BP from a control of 98±5 to 86±3 mm Hg ( P P P P N ^G -nitro- l -arginine methyl ester, an inhibitor of NO synthase. The results strongly suggest that the AT ₂ receptor induces a systemic vasodilator response mediated by NO that counterbalances the vasoconstrictor action of Ang II at the AT ₁ receptor.