EFFECTS OF NITRIC OXIDE ON MYOCRADIAL CONTRACTION-CALCIUM DEPENDENT MECHANISM AND ITS SIGNIFICANTROLEIN ISCHEMIC REPERFUSION MYOCARDIAL DAMAGE

(1)。本研究的主要目的是确定内源性一氧化氮(NO)的抑制是否会增加可逆性缺血后心肌功能障碍，即心肌顿抑。冠脉内注射N-硝基-L-精氨酸(L-NA)对全身血流动力学无明显影响，心肌血流量仅在输注区略有减少但明显减少。与不加入L-NA相比，加入L-NA不仅可增强心内膜下心肌顿抑，还可增强心外膜下心肌顿抑。心肌顿抑的增强与心肌血流量的减少不成比例。因此，抑制NO增强心肌顿抑的机制可能与其对血流的影响无关。本研究的第二个目的是确定抑制NO是否通过钙依赖的机制来增强兴奋性收缩偶联的生理指标之一的早搏后增强效应(PESP)。L-NA对基础LV dp/dt和增强的PESP均无影响，Ryanodine以剂量依赖方式降低PESP，外加CaCl2可部分恢复PESP。在Ryanodine存在下，L-NA可增强CaCl2对基础LV dp/dt的影响，但不增加PESP。抑制NO合成可增强Ryanodine对外源性Ca~(2+)和Gt~(2+)的变力作用，但不能增强PESP，而PESP主要依赖于细胞内Ca~(2+)从肌浆网释放。

(1). The primary goal of the present investigation was to determine whetherinhibition of endogenous nitric oxide (NO) enhances reversible postischemicmyocardial dysfunction, ie, myocardial stunning. Intracoronary administration of N-nitro-L-arginine (L-NA) did not affect systemic hemodynamics, and transmural myocardial blood flow was reduced slightly but significantly only in the infusion territory. Myocardial stunning was enhanced not only in the subendocardium but also in the subepicardiumin in the presence of L-NA compared with the absence of L-NA.The enhancement of myocardial stunning was out of proportion with the reduction of myocardial blood flow. Thus, the mechanism of enhancement of myocardial stunning by inhibition of NO seemed to be potentially independent of its effects on blood flow.(2). The second goal of the present study was to determine whether inhibition of NO enhances post-extrasystolic potentiation (PESP), one of the physiological indices of excitation-contraction coupling, through a Ca^<2+>dependent **echanisum. L-NA neither affected baseline LV dP/dt nor enhanced PESP.Ryanodine diminished PESP in a dose dependent fashion, and an additional CaCl2 partially restoredit. In the presence of ryanodine, the effect of CaCl2 on baseline LV dP/dt was enhanced by L-NA,however, PESP was not enhanced. Inhibition of NO synthesis enhances the inotropic effect of extemal Ca^<2+> in the presence of ryanodine, but does not enhance PESP,which depends mainly upon intracellular Ca^<2+> release from sarcoplasmicreticulm.