title: Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor.
abstract: Cardiovascular risks increase in postmenopausal women. While vitamin D is supplemented for osteoporosis, it is not known whether it protects renal arterial function during estrogen deficiency. Here we measured changes in renovascular reactivity induced by ovariectomy in rats and examined whether calcitriol, the most active form of vitamin D, was able to correct such changes. The impairment of endothelium-dependent relaxation in renal arteries from ovariectomized rats was effectively reversed by long-term calcitriol treatment. It was also corrected by acute exposure to cyclooxygenase-2 (COX-2) inhibitors and a thromboxane-prostanoid receptor antagonist, respectively. Calcitriol normalized the overexpression of COX-2 and thromboxane-prostanoid receptors in intralobal renal artery segments and aortic endothelial cells isolated from ovariectomized rats. In vitro exposure of the arterial segments to calcitriol for 12 h improved relaxation and downregulated thromboxane-prostanoid receptors. The attenuated nitric oxide production in ovariectomized rat aortic endothelial cells was restored following a 12-h treatment with calcitriol, COX-2 inhibition, or thromboxane-prostanoid receptor antagonism. Thus, impaired endothelium-dependent renal artery relaxation in ovariectomized rats is mediated largely through increased activity and expression of COX-2 and the thromboxane-prostanoid receptor. Calcitriol restores endothelial function through downregulating both signaling proteins during estrogen deficiency.
authors: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, and School of Biomedical Sciences, Hong Kong, China.
authors: Jinghui
authors: J
authors: Dong
authors: Siu Ling
authors: SL
authors: Wong
authors: Chi Wai
authors: CW
authors: Lau
authors: Jian
authors: J
authors: Liu
authors: Yi-Xiang
authors: YX
authors: Wang
authors: Zhen
authors: Z
authors: Dan He
authors: Chi
authors: C
authors: Fai Ng
authors: Zhen
authors: Z
authors: Yu Chen
authors: Xiaoqiang
authors: X
authors: Yao
authors: Aimin
authors: A
authors: Xu
authors: Xiaochen
authors: X
authors: Ni
authors: Hongyan
authors: H
authors: Wang
authors: Yu
authors: Y
authors: Huang
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000378:metabolism*; D012077:Renal Artery / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004967:Estrogens; D018167:Receptors, Calcitriol; D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D002117:Calcitriol