title: Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat.
abstract: The available evidence suggests that vitamin D has cardiovascular effects besides regulating calcium homeostasis. To examine the effect of 1,25-dihydroxyvitamin D(3), the major metabolite of vitamin D, on endothelium-dependent contractions, aortic rings of spontaneously hypertensive rats (SHR) were suspended in organ chambers for isometric force measurements. Rings were incubated with N(omega)-nitro-l-arginine methyl ester (l-NAME) and then exposed to increasing concentrations of acetylcholine, ATP, or the calcium ionophore to trigger contractions. This was done in the absence or presence of 1,25-dihydroxyvitamin D(3). The release of prostacyclin after acetylcholine or A-23187 stimulation was also measured. The cytosolic-free calcium concentration was measured by confocal microscopy after incubation with the fluorescent dyes fluo-4 and fura red. The presence of vitamin D receptors was confirmed using immunohistochemistry. Acetylcholine- and ATP-induced endothelium-dependent contractions were significantly reduced compared with those obtained in the absence of the drug. This effect was not present if A-23187 was used as an agonist. The acetylcholine- but not the A-23187-induced release of prostacyclin was reduced by the acute administration of 1,25-dihydroxyvitamin D(3). Exposure to 1,25-dihydroxyvitamin D(3) reduced the increase in cytosolic-free calcium concentration caused by acetylcholine but not by A-23187 in cells. Vitamin D receptors were densely distributed in the endothelium. Inecalcitol (19-nor-14-epi-23-yne-1,25-dihydroxyvitamin D(3)), a synthetic analog of vitamin D, caused a comparable depression of endothelium-dependent contractions as 1,25-dihydroxyvitamin D(3). These results demonstrate that vitamin D(3) modulates vascular tone by reducing calcium influx into the endothelial cells and hence decreasing the production of endothelium-derived contracting factors.
authors.affiliation: Dept. of Pharmacology, Li Ka Shing Faculty of Medicine, Univ. of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Michael S K
authors.initials: MS
authors.lastname: Wong
authors.forename: R
authors.initials: R
authors.lastname: Delansorne
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011464:Epoprostenol / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D014662:Vasoconstrictor Agents; D014807:Vitamin D; D000001:Calcimycin; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D002117:Calcitriol; D000109:Acetylcholine; D002118:Calcium