A Study on the Effect of Nitric Oxide on Myocardial Oxygen Consumption and Cardiac Contractility

我们已经证明，抑制内源性一氧化氮(NO)可增强Emax评估的心肌收缩能力，而其他研究表明，自发的NO供体可引起正性变力作用。在37℃的磷酸盐缓冲溶液中，FK409能自发分解释放NO。本文观察了FK409和8-溴鸟苷-环磷酸(8-BR-cGMP)对α-氯醛糖麻醉犬左室压、容量和左前降支冠脉血流量的影响。左前降支内注入FK409、8-Br-cGMP或罂粟碱，当脑血流量增加并达到峰值时，用一过性下腔静脉结扎测定Emax。在测量Emax之前，两种药物都没有影响心率或左室压。FK409以剂量依赖方式增加脑血流量，降低Emax。8-Br-cGMP以剂量依赖方式增加脑血流量，降低Emax。罂粟碱增加平均脑血流量，但不影响Emax。综上所述，NO降低了体内心肌的收缩能力，而增加了脑血流量。这种作用似乎是由NO的第二信使--环鸟苷一磷酸介导的。

We have shown that inhibition of endogenous nitric oxide (NO) augments cardiac contractility assessed by Emax, whereas others showed that spontaneous NO donors evoke a positive inotropic effect. FK409 decomposes and releases NO spontaneously when dissolved in phosphate buffer solution at 37℃. We examined the effects of FK409 and 8-bromoguanosine-cyclic-monophosphate (8-Br-cGMP) on Emax in α-chloralose-anesthetized dogs instrumented for measurements of left ventricular (LV) pressure and volume and coronary blood flow (CBF) in the left anterior descending artery (LAD). FK409, 8-Br-cGMP or papaverine was infused into the LAD, and Emax was determined by transient inferior vena cava occlusion when CBF was increased and reached its peak. Neither drug affected heart rate or LV pressure just before the measurement of Emax. FK409 increased CBF and decreased Emax in a dose-dependent manner. 8-Br-cGMP increased CBF and decreased Emax in a dose-dependent manner. Papaverine increased mean CBF but did not affect Emax. In conclusion, NO attenuates cardiac contractility in vivo, while increasing CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second messenger of NO.