Angiotensin II responses in at 1A receptor-deficient mice: A role for at 1B receptors in blood pressure regulation
1997.-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 pressor effects of angiotensin II in AgtrlA -/- mice, which lack AT 1A receptors. In enalapril-pretreated AgtrlA -Imice, angiotensin II caused significant and dose-proportional increases in mean arterial pressure. This pressor 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.
Oliverio, MI; Best, CF; Kim, HS; Arendshorst, WJ; Smithies, O; Coffman, TM
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