Mörner S E, Canepari M, Bottinelli R, Cappelli V, Reggiani C
Institute of Human Physiology, University of Pavia, Italy.
Acta Physiol Scand. 1992 Sep;146(1):21-30. doi: 10.1111/j.1748-1716.1992.tb09389.x.
This study analyses the effects of Amrinone (bipyridine derivative with phosphodiesterase inhibitor properties) on the myofibrillar apparatus of rat myocardium. Thin trabeculae were isolated from the right ventricle and chemically demembranated. Force development and shortening velocity were measured during maximal calcium activations (pCa = 4.45) in control conditions and in the presence of 1-3 mM Amrinone. Maximum shortening velocity was obtained both from extrapolation of the force-velocity curve and with the slack test method. Amrinone was found to significantly reduce maximum shortening velocity and force development. Myofibrils and myosin were prepared from rat ventricular myocardium and their ATPase activity was assessed in control conditions and in the presence of Amrinone (0.3-6 mM). Ca-Mg dependent myofibrillar ATPase activity which was determined at low ionic strength was depressed by Amrinone in a dose-dependent way. Ca-stimulated ATPase activity determined at high ionic strength in myofibril or myosin preparations was not affected. Furthermore, Amrinone did not influence the pCa-ATPase activity curve of the myofibrillar preparations. A comparison between the inhibitory effects of Amrinone on myofibrils prepared from euthyroid rats and myofibrils prepared from hypothyroid rats was carried out. The ATPase activity was significantly less depressed in myofibrils prepared from hypothyroid rats than in those prepared from euthyroid rats. These results provide the first evidence of an effect of Amrinone on ATP splitting and force generation in the myofilament system of cardiac muscle.
本研究分析了氨力农（一种具有磷酸二酯酶抑制特性的联吡啶衍生物）对大鼠心肌肌原纤维装置的影响。从右心室分离出细小梁并进行化学去膜处理。在对照条件下以及存在1 - 3 mM氨力农的情况下，于最大钙激活（pCa = 4.45）期间测量力的产生和缩短速度。最大缩短速度通过外力 - 速度曲线外推法和松弛测试法获得。发现氨力农可显著降低最大缩短速度和力的产生。从大鼠心室肌制备肌原纤维和肌球蛋白，并在对照条件下以及存在氨力农（0.3 - 6 mM）的情况下评估其ATP酶活性。在低离子强度下测定的钙 - 镁依赖性肌原纤维ATP酶活性被氨力农以剂量依赖性方式抑制。在肌原纤维或肌球蛋白制剂中高离子强度下测定的钙刺激ATP酶活性未受影响。此外，氨力农不影响肌原纤维制剂的pCa - ATP酶活性曲线。对氨力农对正常甲状腺大鼠制备的肌原纤维和甲状腺功能减退大鼠制备的肌原纤维的抑制作用进行了比较。甲状腺功能减退大鼠制备的肌原纤维中ATP酶活性的降低程度明显低于正常甲状腺大鼠制备的肌原纤维。这些结果首次证明了氨力农对心肌肌丝系统中ATP水解和力产生的影响。
