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(+)/Ca(2+) 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.

Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes

“… 50 have already established that the endothelium-independent relaxation by SNP was damage in streptozotocin-induced T1D (6-weeks duration) in Sprague-Dawley rats, however our T1D model demonstrates that endothelial-independent relaxation induced by SNP was not affected either by alloxan administration or by treatment with sarpogrelate, which allows us to rule out an alteration on the vascular smooth muscle. What is more, these results are in agreement with several authors reporting no impairment in endothelium-independent relaxation 6 51 52 .…”