Schini V B, Vanhoutte P M
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
J Cardiovasc Pharmacol. 1989;14 Suppl 11:S91-4.
The purpose of the present investigations was to determine whether or not SIN-1, a metabolite of molsidomine that spontaneously releases nitric oxide, stimulates the production of adenosine-3',5'-cyclic monophosphate (cyclic AMP) and of guanosine-3',5'-cyclic monophosphate (cyclic GMP) in endothelial cells. All experiments were performed on first or second passage cultured porcine aortic endothelial cells. SIN-1 induced a time- and concentration-dependent accumulation of cyclic GMP but not of cyclic AMP. The production of cyclic GMP evoked by SIN-1 but not evoked by human alpha-natriuretic polypeptide was inhibited by treatment of the cells with either methylene blue (an inhibitor of soluble guanylate cyclase) and hemoglobin (a scavenger of nitric oxide). These data suggest that SIN-1 enhances the activity of soluble guanylate cyclase, which in turn induces the accumulation of cyclic GMP in endothelial cells. This response is probably due to the spontaneous release of nitric oxide, which is a potent activator of soluble guanylate cyclase.
本研究的目的是确定吗多明的代谢产物SIN-1（一种能自发释放一氧化氮的物质）是否刺激内皮细胞中3',5'-环磷酸腺苷（环磷腺苷）和3',5'-环磷酸鸟苷（环磷鸟苷）的产生。所有实验均在第一代或第二代培养的猪主动脉内皮细胞上进行。SIN-1诱导环磷鸟苷呈时间和浓度依赖性积累，但不诱导环磷腺苷积累。用亚甲蓝（一种可溶性鸟苷酸环化酶抑制剂）和血红蛋白（一种一氧化氮清除剂）处理细胞可抑制SIN-1诱导的环磷鸟苷产生，但不抑制人α-利钠肽诱导的环磷鸟苷产生。这些数据表明，SIN-1增强了可溶性鸟苷酸环化酶的活性，进而诱导内皮细胞中环磷鸟苷的积累。这种反应可能是由于一氧化氮的自发释放，一氧化氮是可溶性鸟苷酸环化酶的有效激活剂。
