Angiotensin II responses in AT(1A) receptor-deficient mice: A role for AT(1B) receptors in blood pressure regulation
Angiotensin II responses in AT(1A) receptor-deficient mice: A role for AT(1B) receptors in blood pressure regulation
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DOI：
10.1152/ajprenal.1997.272.4.f515
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发表时间：
1997-04-01
影响因子：
4.2
通讯作者：
Coffman, TM
中科院分区：
文献类型：
--
作者：
Oliverio, MI;Best, CF;Coffman, TM
肾素-血管紧张素系统的大多数经典功能是由1型（AT（1））血管紧张素受体介导的，其中已鉴定出两种亚型，AT（1A）和AT（1B）。然而，这两种AT（1）受体的不同功能很难分开。我们在缺乏AT（1A）受体的Agtr 1A-/-小鼠中检测了血管紧张素II的加压作用。在依那普利预处理的Agtr 1A-/-小鼠中，血管紧张素II导致平均动脉压显著且与剂量成比例增加。这种加压反应不能被预先用交感神经阻滞剂阻断，但能被AT（1）受体拮抗剂氯沙坦和坎地沙坦完全抑制，表明它直接由AT（1B）受体介导。用氯沙坦长期治疗Agtr 1A-/-小鼠，使收缩压从80 +/- 5降至72 +/- 4 mmHg（P < 0.04），表明AT（1B）受体在慢性血压调节中的作用。这些研究首次证明了AT（1B）受体介导的体内升压效应，并证明当AT（1A）受体缺失时，AT（1B）受体有助于调节静息血压。
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.