Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor
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AbstractCardiovascular 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.
All Author(s) ListDong JH, Wong SL, Lau CW, Liu J, Wang YX, He ZD, Ng CF, Chen ZY, Yao XQ, Xu AM, Ni XC, Wang HY, Huang Y
Journal nameKidney International
Detailed descriptionTo ORKTS: doi:10.1038/ki.2013.12
Volume Number84
Issue Number1
Pages54 - 63
LanguagesEnglish-United Kingdom
Keywordscalcitriol; cyclooxygenase-2; estrogen deficiency; renal arteries; thromboxane-prostanoid receptor
Web of Science Subject CategoriesUrology & Nephrology; UROLOGY & NEPHROLOGY

Last updated on 2021-18-06 at 00:22