Studies on the roles for 8-nitroguanosine 3',5'-cyclic monophosphate in the cardiovascular system and the applications to drug discovery.

8-硝基鸟苷3‘，5’-环单磷酸(8-Nitroguanosine 3‘，5’-cGMP)是一种新的生理第二信使，依赖于一氧化氮(NO)的形成。为了研究8-硝基-cGMP在心血管系统中的生理活性，我们研究了它对小鼠主动脉血管反应性的影响。8-Nitro-cGMP可浓度依赖性地增强非糖尿病小鼠主动脉对苯肾上腺素的收缩和松弛作用，但仅对糖尿病小鼠的主动脉起到松弛作用。提示8-NitrocGMP通过eNOS解偶联诱导超氧化物产生可能参与了苯肾上腺素收缩的增强。8-硝基-cGMP的血管扩张作用可能有助于改善糖尿病小鼠的血管内皮功能障碍，为防治糖尿病相关并发症提供了一种新的药理学途径。

8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), formed nitric oxide (NO)-dependently, is a novel physiological second messenger. To study the physiological activity of 8-nitro-cGMP in the cardiovascular system, we studied its effects on vascular reactivity of mouse aortas. 8-Nitro-cGMP induced enhancement of contraction to phenylephrine and relaxation concentration-dependently in aortas from non-diabetic mice, but only relaxation in aortas from diabetic mice. It was suggested that 8-nitrocGMP- induced superoxide production via eNOS uncoupling may mediate the enhancement of the phenylephrine contraction. The vasodilator effect of 8-nitro-cGMP may contribute to amelioration of the vascular endothelial dysfunction in diabetic mice, representing a novel pharmacological approach toprevent the complications associated with diabetes.