Alfacalcidol suppresses α-receptor mediated vasoconstriction via an endothelium dependent mechanism

Aim: Vitamin D level could be related to blood pressure and cardiovascular health. However, the direct suppressor effect of vitamin D on vascular contraction has not yet been explored. Therefore, the effects of alfacalcidol (1α-hydroxyvitamin D3 ) and calcitriol (1α,25- dihydroxyvitamin D3 ) on contractions induced by phenylephrine (10 8 to 10 5 M) in mice aorta were investigated. Materials and methods: Arterial rings were suspended in isolated organ chambers filled with Krebs bicarbonate solution gassed with 95% O2and 5% CO2maintained at 37 °C. Tissue responses were recorded isometrically with a force transducer and displayed on an acquisition system. Alfacalcidol and calcitriol were applied on phenylephrine-induced active tone. Furthermore, aortic rings were preincubated with alfacalcidol and calcitriol and thereafter contracted with phenylephrine. Incubation studies were conducted by endothelium removal and in the presence of L-nitro-arginine methyl ester (L-NAME). Results: Phenylephrine-induced active tones were significantly suppressed by alfacalcidol (P < 0.05 and P < 0.01) and calcitriol (both 10 5 and 10 6 M). The pEC50 values of alfacalcidol and calcitriol were 7.06 ± 0.91 and 7.13 ± 0.60, respectively. Furthermore, preincubation of aortic rings with alfacalcidol (10 5 M) but not calcitriol (10 5 M) significantly inhibited phenylephrine-induced contractions (10 8 to 10 5 M, P < 0.05 and P < 0.001). The suppressive effect of alfacalcidol incubation disappeared with endothelium removal. Furthermore, alfacalcidol was unable to inhibit phenylephrine-induced contractions in the presence of L-NAME, an inhibitor of nitric oxide biosynthesis. Conclusion: In this study we report for the first time that alfacalcidol may prevent phenylephrine-induced vasoconstriction in mice aorta with an endothelium-dependent nitric oxide-mediated mechanism.

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