Myocardial contractile response to nitric oxide and cGMP
Myocardial contractile response to nitric oxide and cGMP
复制标题
DOI：
10.1161/01.cir.93.6.1223
复制
发表时间：
1996-03-15
期刊：
影响因子：
37.8
通讯作者：
Sys, SU
中科院分区：
文献类型：
--
作者：
Mohan, P;Brutsaert, DL;Sys, SU
背景心脏内皮细胞释放许多因子，这些因子可能调节基础心肌的性能。一氧化氮（NO）是血管内皮舒张因子的生物活性物质，通过升高细胞内cGMP而舒张血管平滑肌，可能参与了这种心脏调节。方法和结果我们检测了NO释放的硝基血管舒张剂硝普钠（SNP）、3-吗啉代-悉尼酮亚胺（SIN-1）和S-亚硝基-N-乙酰基-青霉胺（SNAP）对心肌的收缩作用; cGMP类似物，8-溴-cGMP;和cGMP-磷酸二酯酶抑制剂扎普司特在离体猫乳头肌。还研究了内皮细胞（EE）和胆碱能和肾上腺素能刺激对这些效应的调制。添加NO释放硝基血管舒张剂（SNP，SIN-1，SNAP）和8-溴-cGMP的浓度-反应曲线导致双相性肌力反应。虽然低浓度给药诱导正性肌力作用，但较高浓度诱导负性肌力作用。NO诱导的正性和负性肌力作用均被亚甲蓝减弱，表明cGMP的作用。在EE受损的肌肉中，对高浓度8-溴-cGMP的反应向右移动，而胆碱能刺激使曲线向右移动。扎普司特引起了双相浓度依赖性正性肌力作用;损伤EE使曲线的末端部分向上移动。伴随的胆碱能或肾上腺素能刺激修改到负性肌力respons.Conclusions NO和cGMP引起的浓度依赖性双相收缩反应的扎普司特的反应。NO和cGMP的心肌收缩作用受到EE状态和伴随的胆碱能或肾上腺素能刺激的调制。
Background Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation.Methods and Results We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response.Conclusions NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.