Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit.
Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit.
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AT1 受体在血管紧张素 II 重置兔心率压力反射控制中的作用。
DOI：
10.1172/jci116357
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Reid,IA
中科院分区：
文献类型：
--
作者：
Wong,J;Chou,L;Reid,IA
血管紧张素II （Ang II）重置心率的压力反射控制，使血压升高。这种作用显然是通过脑后区域的Ang II受体介导的，但尚不清楚这些受体是AT1还是AT2亚型。在本研究中，研究了选择性AT1受体拮抗剂氯沙坦和选择性AT2拮抗剂PD 123319对长期植入动脉和静脉导管的有意识家兔对Ang II的心脏压力反射反应的影响。静脉滴注苯肾上腺素和硝普赛（2.6 ~ 25微克/千克/分钟）产生血压反射曲线，采用四参数logistic模型分析其上下平台、心率范围中点动脉压（BP50）和斜率系数。从这四个参数出发，计算了反射增益和反射范围。背景：以10 ng/kg / min静脉输注Ang II可使平均动脉压升高17 mmHg，但未改变心率。Ang II使压力反射曲线向右移动，BP50从70.9 +/- 2.0增加到89.3 +/- 2.7 mmHg (P < 0.05)，但没有显著改变压力反射增益。Ang II没有改变压力反射的上平台，但使下平台从119.4 +/- 10.3降至73.6 +/- 11.5 (bpm) (P < 0.05)，使心率范围延长了52.5 bpm。氯沙坦预处理完全消除了对angii的加压反应和心脏压力反射反应。相比之下，PD 123319对这些反应没有影响。单独使用氯沙坦阻断内源性Ang II可使压反射曲线向左移动，BP50从71.2 +/- 2.7降至64.7 +/- 2.5 mmHg （P < 0.05）。这些结果表明，由AT1受体介导的angii对心率调节的重设，内源性angii的基础水平对心脏压力反射施加强直作用，提高压力反射调节心率的设定值。
Angiotensin II (Ang II) resets the baroreflex control of heart rate to a higher blood pressure. This action is apparently mediated via Ang II receptors in the area postrema, but it is not known if these are of the AT1 or AT2 subtype. In the present study the effects of losartan, a selective AT1 receptor antagonist, and PD 123319, a selective AT2 antagonist, on the cardiac baroreflex response to Ang II were investigated in conscious rabbits with chronically implanted arterial and venous catheters. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside (2.6-25 micrograms/kg per min) and analyzed using a four-parameter logistic model to yield their upper and lower plateaus, arterial pressure at the midpoint of the heart rate range (BP50), and slope coefficient. From these four parameters, the gain and range of the baroreflex were calculated. Background intravenous infusion of Ang II at 10 ng/kg per min increased mean arterial pressure by 17 mmHg but did not change heart rate. Ang II shifted the baroreflex curve to the right as indicated by an increase in BP50 from 70.9 +/- 2.0 to 89.3 +/- 2.7 mmHg (P < 0.05), but did not change baroreflex gain significantly. Ang II did not alter the upper plateau of the baroreflex, but decreased the lower plateau from 119.4 +/- 10.3 to 73.6 +/- 11.5 beats per minute (bpm) (P < 0.05), extending the heart rate range by 52.5 bpm. Pretreatment with losartan completely abolished the pressor and cardiac baroreflex responses to Ang II. In contrast, PD 123319 had no effect on these responses. Administration of losartan alone to block endogenous Ang II shifted the baroreflex curve to the left as indicated by a decrease in BP50 from 71.2 +/- 2.7 to 64.7 +/- 2.5 mmHg (P < 0.05). These results demonstrate that the resetting of the baroreflex control of heart rate by Ang II is mediated by AT1 receptors, and that basal levels of endogenous Ang II exert a tonic action on the cardiac baroreflex to increase the setpoint around which the baroreflex regulates heart rate.