Grocott-Mason R, Fort S, Lewis M J, Shah A M
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, United Kingdom.
Am J Physiol. 1994 May;266(5 Pt 2):H1699-705. doi: 10.1152/ajpheart.1994.266.5.H1699.
In isolated myocytes and papillary muscles, both nitric oxide, acting through guanosine 3',5'-cyclic monophosphate (cGMP), and cGMP analogues exert a novel effect on myocardial contraction, influencing mainly the onset of relaxation. We studied the effect of the exogenous nitric oxide donor, sodium nitroprusside (0.1-10 microM), in isolated ejecting guinea pig hearts at constant filling pressure, afterload, and heart rate to identify its direct myocardial effects in the whole heart. Sodium nitroprusside induced concentration-dependent increases in coronary flow as well as premature and faster early left ventricular (LV) pressure decline, but did not change end-diastolic or peak LV pressure or peak rate of rise of LV pressure. There was no correlation between changes in coronary flow and LV pressure decline. Sodium nitroprusside effects were inhibited by hemoglobin, which inactivates nitric oxide. The cGMP-independent vasodilator nicardipine also increased coronary flow but did not influence early LV pressure fall. Thus exogenous nitric oxide exerts novel direct myocardial relaxant effects in the isolated ejecting heart, independent of its known vasodilator activity, and without compromising systolic function.
在分离的心肌细胞和乳头肌中，一氧化氮通过鸟苷3',5'-环磷酸（cGMP）发挥作用，cGMP类似物对心肌收缩均产生一种新的作用，主要影响舒张的起始。我们研究了外源性一氧化氮供体硝普钠（0.1 - 10微摩尔）在恒定充盈压、后负荷和心率条件下对离体射血豚鼠心脏的影响，以确定其在整个心脏中的直接心肌效应。硝普钠引起冠状动脉血流呈浓度依赖性增加，以及左心室（LV）压力过早且更快地下降，但不改变舒张末期或LV峰值压力或LV压力上升的峰值速率。冠状动脉血流变化与LV压力下降之间无相关性。硝普钠的作用被血红蛋白抑制，血红蛋白可使一氧化氮失活。不依赖cGMP的血管扩张剂尼卡地平也增加冠状动脉血流，但不影响LV早期压力下降。因此，外源性一氧化氮在离体射血心脏中发挥新的直接心肌舒张作用，与其已知的血管扩张活性无关，且不损害收缩功能。
