Isaacson J S, Reid I A
Department of Physiology, University of California, San Francisco 94143-0444.
Circ Res. 1990 Mar;66(3):662-71. doi: 10.1161/01.res.66.3.662.
Pharmacological evidence indicates that angiotensin (Ang II) converting enzyme inhibitors attenuate cardiovascular responses to sympathetic stimulation. To investigate the physiological significance of this attenuation, the pressor and heart rate responses to bilateral carotid occlusion (BCO) were studied before and after administration of captopril and again during Ang II replacement in conscious, aortic nerve-sectioned rabbits with chronically implanted carotid occluders. In the control period, BCO produced increases (p less than 0.05) in mean arterial pressure (MAP) and heart rate (HR) of 37.3 +/- 3.0 mm Hg and 21.7 +/- 5.4 beats/min from baseline values of 79.1 +/- 2.5 mm Hg and 255.4 +/- 16.7 beats/min. Captopril (5 mg/kg i.v.) markedly reduced (p less than 0.05) both the pressor (10.2 +/- 2.6 mm Hg) and HR (5.0 +/- 4.0 beats/min) responses to BCO, in parallel with a decrease in plasma Ang II of 75%. Infusion of a subpressor dose of Ang II (5-25 ng/kg/min i.v.) increased plasma Ang II to precaptopril levels and fully restored (p less than 0.05) the pressor (33.0 +/- 5.7 mm Hg) and HR (19.8 +/- 7.7 beats/min) responses to BCO. In two additional series of experiments, the mechanism of the effects of captopril and Ang II were investigated. In the first series, cardiac baroreflex curves (pulse interval versus MAP) were generated by increasing or decreasing blood pressure with phenylephrine or nitroprusside (5-20 micrograms/kg/min i.v.). The slope of the linear region of the curve (2.9 msec/mm Hg) was not changed significantly by captopril treatment (3.1 msec/mm Hg) or Ang II replacement (3.2 msec/mm Hg), indicating that cardiac baroreflex sensitivity was not altered by blockade of the renin-angiotensin system. In the second series, the effect of captopril on the pressor response to exogenous norepinephrine (0.1-2.5 micrograms/kg/min i.v.) was tested. The response was reduced by less than 40%, indicating only a modest postsynaptic component to the action of captopril. These results provide physiological evidence for an important action of endogenous Ang II in facilitating the cardiovascular responses to sympathetic stimulation in conscious rabbits. This facilitation is not due to an action upon the baroreflex per se but results, at least in part, from a presynaptic action of Ang II.
药理学证据表明，血管紧张素（Ang II）转换酶抑制剂可减弱心血管系统对交感神经刺激的反应。为了研究这种减弱作用的生理意义，我们在给清醒的、主动脉神经切断且长期植入颈动脉阻断器的家兔静脉注射卡托普利前后，以及再次给予Ang II替代治疗期间，研究了双侧颈动脉阻断（BCO）引起的升压和心率反应。在对照期，BCO使平均动脉压（MAP）和心率（HR）较基线值[分别为79.1±2.5 mmHg和255.4±16.7次/分钟]升高（p<0.05），MAP升高37.3±3.0 mmHg，HR升高21.7±5.4次/分钟。静脉注射卡托普利（5 mg/kg）显著降低（p<0.05）了BCO引起的升压反应（10.2±2.6 mmHg）和HR反应（5.0±4.0次/分钟），同时血浆Ang II水平降低了75%。输注亚升压剂量的Ang II（5 - 25 ng/kg/分钟，静脉注射）使血浆Ang II升高至卡托普利给药前水平，并完全恢复（p<0.05）了BCO引起的升压反应（33.0±5.7 mmHg）和HR反应（根据英文原文推测此处应为19.8±7.7次/分钟）。在另外两组实验中，研究了卡托普利和Ang II作用的机制。在第一组实验中，通过静脉注射去氧肾上腺素或硝普钠（5 - 20 μg/kg/分钟）升高或降低血压来绘制心脏压力感受性反射曲线（脉搏间期与MAP）。卡托普利治疗组（斜率为3.1毫秒/mmHg）或Ang II替代治疗组（斜率为3.2毫秒/mmHg）的曲线线性区域斜率（2.9毫秒/mmHg）均未发生显著变化，这表明肾素 - 血管紧张素系统被阻断后，心脏压力感受性反射敏感性未改变。在第二组实验中，测试了卡托普利对外源性去甲肾上腺素（0.1 - 2.5 μg/kg/分钟，静脉注射）升压反应的影响。该反应降低幅度小于40%，表明卡托普利的作用仅具有适度的突触后成分。这些结果为内源性Ang II在促进清醒家兔心血管系统对交感神经刺激反应中的重要作用提供了生理学证据。这种促进作用并非源于对压力感受性反射本身的作用，至少部分是由于Ang II的突触前作用所致。
