The endothelium plays a crucial role in maintaining vascular homeostasis by producing several vasodilating factors, including nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarisation (EDH); however, the balance between endothelial relaxing and contracting factors is disrupted in disease states such as diabetes mellitus and hypertension. Most reported studies of endothelial dysfunction in diabetes focused on the actions of NO; however, there is accumulating evidence demonstrating that in addition to NO, PGI2 and EDH are likely to contribute to the vasodilatation of blood vessels. EDH plays an important role as a regulator of vascular tone and reactivity in resistance and conduit arteries of animal models and humans. PGI2 only plays a minimal role in endothelium-dependent vasodilatation but may serve as an important compensatory mechanism in conditions in which NO and EDH activities are decreased. Further studies are needed to determine the exact roles of EDH and PGI2 in the development of endothelial dysfunction and clinical vasculopathy in humans with type 1 and type 2 diabetes.

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.