Murakami H, Liu J L, Zucker I H
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198-4575, USA.
Hypertension. 1997 Feb;29(2):564-9. doi: 10.1161/01.hyp.29.2.564.
Enhanced sympathetic outflow is seen in both patients with congestive heart failure and animals with experimental heart failure. In a previous study, we demonstrated that the baroreflex control of heart rate was impaired in conscious rabbits with pacing-induced heart failure and that this impairment was partially restored by blockade of angiotensin II type 1 (AT1) receptors. In the present study, we determined the interaction between the renin-angiotensin system and baroreflex control of renal sympathetic nerve activity in normal conscious rabbits and conscious rabbits with pacing-induced heart failure before and after AT1 receptor blockade. Heart failure was induced by rapid ventricular pacing at a rate of 360 to 380 beats per minute for an average of 16.7 +/- 0.6 days. To generate baroreflex curves, we altered arterial pressure by administering phenylephrine and sodium nitroprusside. A sigmoidal logistic function was fit to renal sympathetic nerve activity-mean arterial pressure relationships for analysis of several components of baroreflex function. AT1 receptors were blocked by intravenous administration of the specific antagonist L-158,809. In normal rabbits, there was no significant difference in any parameter of baroreflex function before and after blockade of AT1 receptors. In contrast, blockade of AT1 receptors enhanced baroreflex sensitivity in heart failure rabbits. The maximal gain increased to 5.0 +/- 0.7% renal sympathetic nerve activity/mm Hg from 2.6 +/- 0.3 (P < .05). Although L-158,809 had no effect on baseline renal sympathetic nerve activity in normal rabbits, analysis of the data in the heart failure rabbits indicated that baseline renal sympathetic nerve activity was reduced from 33 +/- 5% to 17 +/- 4% after L-158,809 administration after adjustment for changes in arterial pressure. These data suggest that angiotensin II plays a role in baroreflex impairment in this model of heart failure and may be in part responsible for the depressed baroreflex sensitivity observed in heart failure.
充血性心力衰竭患者和实验性心力衰竭动物均出现交感神经输出增强。在先前的一项研究中，我们证明，起搏诱导的心力衰竭清醒兔的心率压力反射控制受损，并且通过阻断1型血管紧张素II（AT1）受体可部分恢复这种损伤。在本研究中，我们确定了正常清醒兔和起搏诱导的心力衰竭清醒兔在AT1受体阻断前后肾交感神经活动的肾素 - 血管紧张素系统与压力反射控制之间的相互作用。通过以每分钟360至380次的速率快速心室起搏平均16.7±0.6天来诱导心力衰竭。为了生成压力反射曲线，我们通过给予去氧肾上腺素和硝普钠来改变动脉血压。将S形逻辑函数拟合到肾交感神经活动 - 平均动脉压关系，以分析压力反射功能的几个组成部分。通过静脉内给予特异性拮抗剂L-158,809来阻断AT1受体。在正常兔中，AT1受体阻断前后压力反射功能的任何参数均无显著差异。相比之下，阻断AT1受体可增强心力衰竭兔的压力反射敏感性。最大增益从2.6±0.3增加到5.0±0.7％肾交感神经活动/ mmHg（P <.05）。虽然L-158,809对正常兔的基线肾交感神经活动没有影响，但对心力衰竭兔的数据分析表明，在调整动脉压变化后，给予L-158,809后基线肾交感神经活动从33±5％降至17±4％。这些数据表明，血管紧张素II在这种心力衰竭模型的压力反射损伤中起作用，并且可能部分负责心力衰竭中观察到的压力反射敏感性降低。
