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Calcitriol inhibits COX-1 and COX-2 expressions of renal vasculature in hypertension: Reactive oxygen species involved?

Vitamin D modulates about 3% human gene transcription besides the classical action on calcium/phosphorus homeostasis. The blood pressure-lowing and other protective action on cardiovascular disease have been reported. The present study aims to examine whether COX-1 and COX-2 were implicated in endot...

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Published in:Clinical and experimental hypertension (1993) 2021-01, Vol.43 (1), p.91-100
Main Authors: Suo, Zizheng, Liu, Yanzhi, Li, Yueyi, Xu, Cong, Liu, Yuhan, Gao, Mingming, Dong, Jinghui
Format: Article
Language:English
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Summary:Vitamin D modulates about 3% human gene transcription besides the classical action on calcium/phosphorus homeostasis. The blood pressure-lowing and other protective action on cardiovascular disease have been reported. The present study aims to examine whether COX-1 and COX-2 were implicated in endothelial dysfunction in hypertension and calcitriol, an active form of vitamin D preserved endothelial function through regulating COX expression. Isometric study demonstrated the impaired endothelium-dependent relaxation (EDR) in renal arteries from spontaneously hypertensive rats were reversed by 12 h-calcitriol treatment and COX-1 and COX-2 inhibitors. Combined uses of COX-1 and COX-2 inhibitor induced more improved relaxations. Exaggerated expressions of COX-1 and COX-2 in renal artery from SHR were inhibited by 12 h-administration of calcitriol, NADPH oxidase inhibitor DPI, or reactive oxygen species (ROS) scavenger tempol. Furthermore, in normotensive WKY rats, calcitriol prevents against the blunted EDR in renal arteries by 12 h-Ang II exposure, with similar improvements by COX-1 and COX-2 inhibitors. Accordingly, increased COX-1 and COX-2 expressions by Ang II exposure were corrected by losartan, DPI, or tempol. Studies on human renal artery also revealed the beneficial action of calcitriol is mediated by suppressing COX-1 and COX-2 expressions, dependent on vitamin D receptor (VDR) activation. Taken together, our findings showed that COX-1 and COX-2 are positively involved in the renovascular dysfunction in hypertension and via VDR, calcitriol benefits renovasular function by suppressing COX-1 and COX-2 expressions. Furthermore, ROS is involved in the COX-1 and COX-2 up-regulations of renal arteries, maybe serving as a mediator in the inhibitory action of calcitriol on COX expression.
ISSN:1064-1963
1525-6006
DOI:10.1080/10641963.2020.1817473