Wong J, Chou L, Reid I A
Department of Physiology, University of California, San Francisco 94143-0444.
J Clin Invest. 1993 Apr;91(4):1516-20. doi: 10.1172/JCI116357.
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.
血管紧张素II（Ang II）将心率的压力感受性反射控制重置为更高的血压水平。这一作用显然是通过最后区的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，在长期植入动脉和静脉导管的清醒兔中，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Ang II心脏压力感受性反射反应的影响。通过静脉输注去氧肾上腺素和硝普钠（2.6 - 25微克/千克每分钟）生成压力感受性反射曲线，并使用四参数逻辑模型进行分析，以得出其上、下平台期、心率范围中点的动脉血压（BP50）和斜率系数。根据这四个参数，计算压力感受性反射的增益和范围。以每分钟10纳克/千克的速度静脉输注Ang II作为背景，可使平均动脉压升高17毫米汞柱，但不改变心率。Ang II使压力感受性反射曲线右移，BP50从70.9±2.0毫米汞柱增加到89.3±2.7毫米汞柱（P < 0.05），但压力感受性反射增益无显著变化。Ang II未改变压力感受性反射的上平台期，但使下平台期从每分钟119.4±10.3次心跳降至73.6±11.5次心跳（P < 0.05），使心率范围扩大52.5次/分钟。氯沙坦预处理完全消除了对Ang II的升压和心脏压力感受性反射反应。相比之下，PD 123319对这些反应无影响。单独给予氯沙坦阻断内源性Ang II可使压力感受性反射曲线左移，BP50从71.2±2.7毫米汞柱降至64.7±2.5毫米汞柱（P < 0.05）。这些结果表明，Ang II对心率压力感受性反射的重置是由AT1受体介导的，内源性Ang II的基础水平对心脏压力感受性反射发挥紧张性作用，以提高压力感受性反射调节心率的设定点。
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