Vitamin D3 does not augment EDHF-mediated relaxations to bradykinin

Abstract

The most active metabolite of vitamin D, 1, 25-dihydroxyvitamin D3 acutely reduces endothelium-dependent contractions to acetylcholine by reducing the increase in calcium concentration caused by the muscarinic agonist in the endothelial cells. The release of endothelium-derived hyperpolarizing factor involves calcium-dependent potassium channels. Thus, vitamin D3 may also affect endothelium-dependent relaxations by regulating EDHF-mediated responses. The present experiments were designed to investigate the effect of acute treatment of vitamin D3 on the EDHF pathway. Rings of porcine coronary arteries, with endothelium, were suspended in organ chambers for isometric tension recording. To study the EDHF mediated relaxation, quiescent rings were incubated with L-NAME (nitric oxide synthase inhibitor, 10-4 M) and indomethacin (cyclooxygenase inhibitor, 10-5 M) for 40 minutes. They were contracted with prostaglandin F2α and then relaxed with cumulatively increasing concentrations of bradykinin. The experiments were carried out in the presence or absence of 10-7 M 1,25-dihydroxyvitamin D3. The results show that the relaxation induced by bradykinin was not altered significantly by the prior incubation of 1,25-dihydroxyvitamin D3, suggesting that vitamin D3 does not have an regulatory effect on EDHF-mediated responses. Thus the vascular protective effect of vitamin D is probably due to a reduction of endothelium-dependent contractions.