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

Authors: İSMAİL ÜN, AKİF HAKAN KURT, ALİ BATUŞ, KANSU BÜYÜKAFŞAR

Abstract: 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 (1\alpha-hydroxyvitamin D_3) and calcitriol (1\alpha,25-dihydroxyvitamin D_3) 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% O_2 and 5% CO_2 maintained 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 pEC_{50} 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.

Keywords: Alfacalcidol, calcitriol, mice, aorta, contraction

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