Na⁺/Ca²⁺ Exchanger Inhibitor Restores Endothelium-dependent Relaxation in Diabetic Rat Aorta

Abstract

The aims of this study were to examine the effects of KB-R7943, an inhibitor of Na⁺/Ca²⁺ exchanger, on the endothelium-dependent relaxation (EDR) in diabetic rat aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured in aortic rings of nondiabetic and streptozotocin-diabetic rats. Diabetes mellitus was induced by single injection of streptozotocin (60 mg/kg). The treated rats received 0.01 or 0.1 mg/kg/day of KB-R7943 for 8 weeks. ACh-induced relaxation was impaired in diabetic compared to control rings and the vasodilatation to SNP was unaffected. Treatment with KB-R7943 markedly enhanced relaxation to ACh in diabetic but not in control rings. KB-R7943 significantly increased superoxide dismutase (SOD) activity and the nitric oxide (NO) release. These results suggest that KB-R7943 can restore impaired EDR in aortic rings of diabetic rats, which may be related to scavenging oxygen free radicals and enhancing NO production.

Key words

endothelium-dependent relaxation - diabetic rat - Na⁺/Ca²⁺ exchanger - superoxide dismutase - nitric oxide

^* Xiu-fen Li and Ting-ting Wan contributed equally to this study.

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