Cheng C P, Suzuki M, Ohte N, Ohno M, Wang Z M, Little W C
Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1045, USA.
Circ Res. 1996 May;78(5):880-92. doi: 10.1161/01.res.78.5.880.
Alterations in the cardiac response to angiotensin II (Ang II) may contribute to the functional impairment in tachycardia-induced heart failure (congestive heart failure [CHF]). Accordingly, we studied the response to Ang II in eight conscious instrumented dogs before and after inducing CHF. Left ventricular (LV) performance was assessed by measuring LV pressure and LV volume. Isolated myocyte function was evaluated using computer-assessed videomicroscopy. In conscious animals before CHF, Ang II produced a load-dependent slowing of the time constant of LV relaxation (tau) and did not depress intact LV contractile function. After CHF, although Ang II produced a similar increase in LV systolic pressure, the increases in LV diastolic pressure and time constant tau were much greater, and contractile performance was depressed. These changes persisted when the elevation of end-systolic pressure was prevented by nitroprusside. Similar changes were also present after autonomic blockade. In isolated myocytes, before CHF, Ang II (10(-6) mol/L) produced a slight positive inotropic effect. In contrast, after CHF, Ang II produced a negative inotropic effect and slowed the rate of relengthening. The effects in the intact LV and myocytes were reversed by an Ang II AT1 receptor blocker (losartan). We conclude that pacing-induced CHF alters the LV and myocyte response to Ang II, so that Ang II produces direct depressions in intact LV contraction, relaxation, and filling and exacerbates myocyte contractile dysfunction. These effects are mediated through the activation of AT1 receptors.
心脏对血管紧张素II（Ang II）反应的改变可能导致心动过速诱发的心力衰竭（充血性心力衰竭[CHF]）中的功能损害。因此，我们研究了八只清醒的植入仪器的犬在诱导CHF前后对Ang II的反应。通过测量左心室（LV）压力和LV容积来评估LV功能。使用计算机辅助视频显微镜评估分离的心肌细胞功能。在清醒的CHF前动物中，Ang II导致LV舒张时间常数（tau）呈负荷依赖性减慢，且未降低完整LV的收缩功能。CHF后，尽管Ang II使LV收缩压有类似程度的升高，但LV舒张压和时间常数tau的升高幅度更大，且收缩功能降低。当硝普钠防止收缩末期压力升高时，这些变化仍然存在。自主神经阻滞后也出现类似变化。在分离的心肌细胞中，CHF前，Ang II（10^(-6) mol/L）产生轻微的正性肌力作用。相反，CHF后，Ang II产生负性肌力作用并减慢再延长速率。Ang II AT1受体阻滞剂（氯沙坦）可逆转完整LV和心肌细胞中的这些作用。我们得出结论，起搏诱导的CHF改变了LV和心肌细胞对Ang II的反应，因此Ang II直接降低完整LV的收缩、舒张和充盈功能，并加剧心肌细胞收缩功能障碍。这些作用是通过AT1受体的激活介导的。
