Vasodilator effects of cromakalim and HA 1077 in diabetic rat aorta
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BACKGROUND: Impairment of the vasorelaxant responses have been reported in diabetes mellitus. In this study, the roles of the K-ATP channel and rho kinase pathway were evaluated by using the K-ATP channel opener cromakalim and Rho-kinase inhibitor HA 1077 in diabetic rat aorta. METHODS: Adult male Wistar rats weighing (250-300 g) were divided into diabetic and control groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg/i.p). RESULTS: Vasodilator responses induced by cromakalim ;(10(-7) to 10(-3)M) and HA 1077 (10(-6) to 10(-4)M) were significantly less in diabetic rings compared with control rings (p<0.01). The decrease in the relaxant effect of cromakalim was more in endothelium-denuded rings compared to the endothelium-intact rings (p<0.05). There were no significant differences between endothelium intact and non-intact rings in the presence of HA 1077. When two drugs were administered together, relaxation was significantly less than with seperate administration of each drug in the diabetic group (p<0.01). Pre-treatment with N omega-nitro-L-arginine methylester (L-NAME) (10(-6) to 10(-4) M), an NO synthase inhibitor, significantly decreased the relaxant response to cromakalime and HA 1077 in both the control and diabetic groups (p<0.05). CONCLUSIONS: These results suggest that the impaired relaxant effects were further decreased depending on KATP channel activity but the effects of Rho-kinase enzyme inhibitors on relaxation responses were not significantly changed in diabetes mellitus.