Alphacalcidol Supplementation Improves Acetylcholine-Mediated Relaxation in Aorta of Diabetic Rats on Vitamin D-Deficient Diet
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Abstract
Introduction: Vitamin D deficiency has been implicated as one of the factors involved in endothelial dysfunction associated with diabetes. This study aimed to evaluate the effects of active vitamin D (alphacalcidol) supplementation on aortic endothelial function in diabetic rats receiving vitamin D-deficient diet. Methods: Streptozotocin-induced diabetic rats were fed with standard diet (D) or vitamin D-deficient diet (DD and DDS) for 10 weeks. Group DDS was then supplemented with 0.2 μg/kg alphacalcidol at the last four weeks of the study duration. Non-diabetic rats were fed with standard diet (N) or vitamin-D deficient diet (ND). At the end of the experiment, the rats were sacrificed, and their aortic rings were harvested for endothelial functional study. Results: Acetylcholine-induced relaxation in aorta of diabetic rats (D and DD) were significantly lower compared to non-diabetic rats (N). In the presence of endothelial nitric oxide synthase blocker (L-NAME), maximal relaxation induced by acetylcholine in aorta of D and DD groups were significantly higher compared to N, ND and DDS groups, indicating involvement of non-nitric oxide (NO) relaxation pathways in diabetes. Four weeks supplementation with alphacalcidol in DDS group significantly improved acetylcholine-induced relaxation and reduced the reliance on non-NO relaxation pathways. Conclusion: The present study suggests that impairment of acetylcholine-induced relaxation in aorta of diabetes and diabetes with vitamin D-deficient diet was largely due to a decrease in NO related pathways, and this was compensated by non-NO pathways. Supplementation with alphacalcidol alleviated endothelial impairment in aorta of diabetic rats with vitamin D-deficient diet.
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