Grocott-Mason R, Anning P, Evans H, Lewis M J, Shah A M
Department of Cardiology, University of Wales College of Medicine, Cardiff, United Kingdom.
Am J Physiol. 1994 Nov;267(5 Pt 2):H1804-13. doi: 10.1152/ajpheart.1994.267.5.H1804.
Nitric oxide (NO) modulates myocardial contractile behavior in several isolated preparations, e.g., cardiac myocytes and papillary muscles, via elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently reported that the exogenous NO donor, sodium nitroprusside, selectively modulates left ventricular (LV) relaxation in the isolated ejecting guinea pig heart, independent of coronary flow. We now report the effects of endogenously released NO on LV performance in this preparation (constant heart rate and loading). Both bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV relaxation (maximum change in time constant, tE, -10.5 +/- 1.6 and -13.4 +/- 2.1%, respectively; both P < 0.05), without significantly altering early systolic parameters (e.g., rate of LV pressure development). These effects were inhibited by hemoglobin (P < 0.05; n > or = 6), which inactivates NO. Bradykinin (100 nM, n = 10) had an additional negative inotropic effect, which was not inhibited by hemoglobin. Neither agonist altered relaxation in isolated papillary muscles. These data suggest that endogenous NO, probably released from coronary microvascular endothelial cells, modulates LV relaxation in the intact heart.
一氧化氮（NO）通过提高细胞内鸟苷3'，5'-环磷酸（cGMP）水平，在几种离体标本（如心肌细胞和乳头肌）中调节心肌收缩行为。我们最近报道，外源性NO供体硝普钠在离体射血豚鼠心脏中可选择性调节左心室（LV）舒张，且与冠状动脉血流无关。我们现在报告内源性释放的NO对该标本（恒定心率和负荷）中左心室功能的影响。缓激肽（1 nM，n = 6）和P物质（100 nM，n = 6）均加速了左心室早期舒张（时间常数tE的最大变化分别为-10.5 +/- 1.6%和-13.4 +/- 2.1%；P均< 0.05），而未显著改变早期收缩参数（如左心室压力上升速率）。这些效应被血红蛋白抑制（P < 0.05；n≥6），血红蛋白可使NO失活。缓激肽（100 nM，n = 10）还有额外的负性肌力作用，该作用未被血红蛋白抑制。两种激动剂均未改变离体乳头肌的舒张。这些数据表明，内源性NO可能从冠状动脉微血管内皮细胞释放，在完整心脏中调节左心室舒张。
