Angiotensin II responses in AT(1A) receptor-deficient mice: A role for AT(1B) receptors in blood pressure regulation

Most of the classic functions of the renin-angiotensin system are mediated by type 1 (AT(1)) angiotensin receptors, of which two subtypes, AT(1A) and AT(1B), have been identified. However, distinct functions for these two AT(1) receptors have been difficult to separate. We examined the presser effects of angiotensin II in Agtr1A -/- mice, which lack AT(1A) receptors. In enalapril-pretreated Agtr1A -/- mice, angiotensin II caused significant and dose-proportional increases in mean arterial pressure. This presser response was not blocked by pretreatment with sympatholytic agents but was completely inhibited by the AT(1)-receptor antagonists, losartan and candesartan, suggesting that it is directly mediated by AT(1B) receptors. Chronic treatment of Agtr1A -/- mice with losartan reduced systolic blood pressure from 80 +/- 5 to 72 +/- 4 mmHg (P < 0.04), suggesting a role for AT(1B) receptors in chronic blood pressure regulation. These studies provide the first demonstration of in vivo pressor effects mediated by AT(1B) receptors and demonstrate that, when AT(1A) receptors are absent, the AT(1B) receptor contributes to the regulation of resting blood pressure.