Moravec C S, Schluchter M D, Paranandi L, Czerska B, Stewart R W, Rosenkranz E, Bond M
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio 44195-5069.
Circulation. 1990 Dec;82(6):1973-84. doi: 10.1161/01.cir.82.6.1973.
The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
利用来自衰竭心脏和功能正常心脏的分离小梁肌，研究了血管紧张素II（Ang II）对人心肌的直接作用。对心房和心室小梁进行了研究。结果表明，Ang II对人心肌有正性肌力作用。各组间Ang II作用的比较表明，与衰竭心肌相比，心房和正常心肌的反应性往往更高。本研究结果还表明，人肌肉对Ang II的反应性存在异质性，且与患者年龄、性别、诊断、既往血管紧张素转换酶抑制剂治疗情况或心功能无关。在衰竭的心室小梁中，Ang II反应与异丙肾上腺素反应之间存在显著相关性，这可能表明衰竭人心室中β-肾上腺素能反应性缺陷伴随着对Ang II反应性的丧失。研究扩展至叙利亚心肌病仓鼠及其对照。正常仓鼠心室肌出现剂量依赖性正性肌力反应，但心肌病仓鼠心肌的反应显著减弱。Ang II未缩短收缩时间，用肾上腺素能阻滞剂预处理也未使剂量-反应曲线移位，表明该反应不是由环磷酸腺苷介导的。本研究首次证明Ang II可直接对人心肌发挥正性肌力作用，并证实Ang II对仓鼠心肌有直接作用。然而，该研究进一步表明，心肌对Ang II的正性肌力反应是异质性的，且可能因心力衰竭而减弱。
