Carvedilol ameliorates endothelial dysfunction in streptozotocin-induced diabetic rats

Guo-Sheng Fu, He Huang, Fei Chen, Hui-Ping Wang, Ling-Bo Qian, Xi-Ye Ke, Qiang Xia
European Journal of Pharmacology 2007 July 19, 567 (3): 223-30
The beta-blocker, carvedilol has an additional endothelium-dependent vasodilating properties in patients with hypertension or heart failure. Whether carvedilol can improve endothelium-dependent relaxation in a diabetic animal model and its mechanism of action are unknown. The aim of this study was to investigate the effect of carvedilol on the endothelial-response of aortas from diabetic rats and the underlying mechanism. Acetylcholine-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, and expression of nitric oxide synthase 3 (NOS3) mRNA were measured in aortas isolated from both non-diabetic and streptozotocin-induced diabetic rats. The level of NO in serum was also measured 5 weeks after carvedilol administration (1 or 10 mg/kg/day). Endothelium-dependent relaxation declined along with the decrease of serum NO level in aortas from diabetic rats. Treatment with carvedilol for 5 weeks prevented the inhibition of endothelium-dependent relaxation and the decrease of serum NO levels caused by diabetes. The expression of NOS3 mRNA, protein expression and NOS3 phosphorylation at Ser1177 in diabetic rat aorta was very low in untreated diabetic aortas compared with the healthy group. Administration of carvedilol not only significantly increased the expression of NOS3 mRNA but also protein expression and NOS3 phosphorylation at Ser1177 in the healthy and diabetic groups. In conclusion, chronic carvedilol administration significantly ameliorated the endothelial dysfunction in diabetic rat aortas, in which increased NO level, up-regulated NOS3 mRNA and phosphorylation at Ser1177 may be involved.

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