Enalapril and valsartan improved enhanced CPA-induced aortic contractile response in type 2 diabetic rats by reduction in TRPC4 protein level

Abstract

Background and objective: Enalapril and valsartan have been used to treat vascular complications in diabetes. Considering the role of disturbed calcium hemostasis in vascular dysfunction in diabetes,the aim of this study was to evaluate the effects of enalapril and valsartan on vascular response in type 2 diabetic rats in relation to store-operated calcium entry and TRPC4 protein level and function. Methodology: Male Spargue-Dawley diabetic rats (n = 6 group−1) were received distilled water,enalapril (20 mg kg−1 day−1) or valsartan (20 mg kg−1 day−1) for 6 weeks. Non-diabetic control rats were received distilled water for 6 weeks. Cyclopiazonic acid (CPA)-induced contractile response was measured in rat aortic rings in the presence and absence of ML204 (2.6 μM),a TRPC4 channel blocker. In addition,TRPC4 levels were measured in thoracic aorta using western immunoblotting method. Results: The CPA-induced contraction of vascular smooth muscle cell of aorta was significantly higher in diabetic control group as compared to non-diabetic rats. Enalapril and valsartan decreased aortic contractile response to CPA in diabetic rats to a level comparable to non-diabetic rats. The ML204 decreased aortic contraction in response to CPA in all studied groups in comparison to their relevant controls,although non-significant. The TRPC4 protein levels were significantly increased in aorta vascular smooth muscle cells of diabetic control group as compared to nondiabetic rats. Enalapril and valsartan significantly decreased TRPC4 protein levels in diabetic rats in comparison to diabetic control group. Conclusion: These findings suggest that enalapril and valsartan modify abnormal vascular response in diabetic rats through their effects on store-operated calcium entry which could be partially attributed to their effects on TRPC4 channels expression.