Chronic treatment of vitamin D derivatives reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Abstract

The available evidences suggest that vitamin D has cardiovascular effects besides regulating calcium homeostasis. Previous studies demonstrated that 1,25-dihydroxyvitamin D3, the major metabolite of vitamin D, acutely reduce endothelium-dependent contractions induced by acetylcholine. To examine the chronic effect of 1,25-dihydroxyvitamin D3, rats were treated with the vitamin D derivative for 6 weeks. The serum 1,25-dihydroxyvitamin D3 level was significantly higher than the control while the mean arterial blood pressure was significantly lower. Aortic rings with or without endothelium were used for organ bath experiments. The release of prostacyclin and thromboxane A2 after acetylcholine or A23187 stimulation were measured. The cytosolic-free calcium concentration was measured by confocal microscopy with the fluorescent dyes Fluo-4. Real time PCR was used to compare the mRNA level of COX-1, prostacyclin synthase, thromboxane synthase and eNOS between the control and treated groups. Both acetylcholine- and A23187-induced endothelium-dependent contractions were reduced significantly in the treated group. The acetylcholine-induced release of prostacyclin and the A23187-induced thromboxane A2 was reduced in the treated group. There was no significant difference in cytosolic free calcium concentration caused by acetylcholine or A23187 between control and treated groups. COX-1 mRNA level was significantly inhibited in the treated SHR. These results demonstrate that chronic treatment of 1,25-dihydroxyvitamin D3 modulates vascular tone by inhibiting the expression level of COX-1 mRNA which is a completely different mechanism as in the acute treatment. This chronic effect to EDCF may account for one of the factors that reducing the mean arterial blood pressure in the SHR rats.