Aminoguanidine inhibits aortic hydrogen peroxide production, VSMC NOX activity and hypercontractility in diabetic mice

作者：Oak Jeong Ho; Youn Ji Youn; Cai Hua^*

来源：Cardiovascular Diabetology, 2009, 8(1): 65.

DOI：10.1186/1475-2840-8-65

Background: Dysfunctionally uncoupled endothelial nitric oxide synthase (eNOS) is involved in producing reactive oxygen species (ROS) in the diabetic endothelium. The present study investigated whether anti-diabetes drug Aminoguanidine (AG) has any effect on eNOS function and vascular oxidant stress. Methods and Results: Blood glucose levels were increased to 452.0 /- 15.1 mg/dl in STZ-treated male C57BL/6J mice (148.4 /- 3.2 mg/dl in untreated controls). Aortic productions of NO(center dot) and O(2)(center dot-) were measured specifically and sensitively using electron spin resonance. Diabetic mice had a marked increase in aortic O(2)(center dot-) production. Aortic hydrogen peroxide (H(2)O(2)) production was also increased in diabetic aortas and significantly attenuated by AG. AG however had only a marginal effect in reducing aortic O(2)(center dot-) production, which corresponded to a minimal effect in improving aortic nitric oxide (NO(center dot)) bioavailability. The endothelium-dependent vasodilatation however was modestly but significantly improved by AG, likely consequent to AG-induced reduction in hypercontractility. NAD(P) H oxidase (NOX)- dependent O(2)(center dot-) production was completely attenuated by AG in endothelium-denuded diabetic aortas. Conclusion: In summary, despite that AG is not an effective eNOS recoupling agent presumably consequent to its ineffectiveness in preventing endothelial NOX activation, it is inhibitory of aortic H(2)O(2) production, VSMC NOX activity, and hypercontractility in diabetes.

• 出版日期2009-12-30