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一氧化氮合酶(nitric oxide synthase,NOS)系统对正常或应激状态下心脏电-机械活动起着复杂的调控作用。本研究采用心肌细胞收缩与钙瞬变同步检测手段,研究NOS系统对心肌细胞收缩的潜在调控机制。在急性分离的正常大鼠心室肌细胞,100μmol/L spermidine选择性抑制神经源性一氧化氮合酶(neuronal NOS,nNOS)显著加强了细胞的收缩活动[正常对照组:(10.5±0.21)%;nNOS抑制组:(12.4±0.18)%]与内质网的钙释放[正常对照组:(0.27±0.03)%;nNOS抑制组:(0.42±0.01)%],但是延缓了心肌细胞的舒张[正常对照组:(25.2±1.3)ms;nNOS抑制组:(53±2.8)ms]与内质网的钙回收[正常对照组:(129±4.3)ms;nNOS抑制组:(176±7.1)ms]。该效应与30μmol/L dynasore抑制内陷调节蛋白——发动蛋白的结果类似。NO供体S-Nitroso-N-acetylpenicillamine(SNAP)可以缓解nNOS抑制或发动蛋白抑制所致的收缩与内质网钙释放加强的效应。结果表明,nNOS系统对心脏机械活动的调节可能部分涉及发动蛋白介导的内陷机制。
The nitric oxide synthase (NOS) system plays a complex regulatory role in cardiac electrical-mechanical activity under normal or stress conditions. In this study, synchronous detection of myocardial contraction and calcium transients were used to investigate the potential regulatory mechanism of NOS on cardiomyocyte contraction. In acutely isolated normal rat ventricular myocytes, selective inhibition of neuronal nitric oxide synthase (nNOS) by 100 μmol / L spermidine significantly enhanced the contractile activity of the cells [normal control group: (10.5 ± 0.21)% ; nNOS inhibition group: (12.4 ± 0.18)%] and endoplasmic reticulum calcium release [normal control group (0.27 ± 0.03)%; nNOS inhibition group: (0.42 ± 0.01)%], but delayed the relaxation of myocardial cells (N = 25), normal control group (25.2 ± 1.3) ms, nNOS inhibition group (53 ± 2.8) ms and endoplasmic reticulum calcium recovery ) ms]. This effect is similar to the inhibition of intimal regulatory protein-motor protein by 30 μmol / L dynasore. NO-donor S-Nitroso-N-acetylpenicillamine (SNAP) attenuated the effect of nNOS inhibition or corticotropin-induced contraction and increased endoplasmic reticulum calcium release. The results show that the regulation of cardiac mechanical activity by the nNOS system may be partially involved in the dynamin-mediated invagination mechanism.