title: Calcitriol protects renovascular function in hypertension by down-regulating angiotensin II type 1 receptors and reducing oxidative stress.
abstract: OBJECTIVE
  The present study investigated whether or not calcitriol, an active form of vitamin D, protects against renovascular dysfunction in hypertension and, if so, whether or not such protection alters the expression of key proteins involved in that dysfunction.
  
  
  RESULTS
  Changes in isometric tension showed that the impaired endothelium-dependent relaxations in renal arteries of hypertensive patients were enhanced by 12 h in vitro treatment with calcitriol. Dihydroethidium fluorescence revealed an elevated level of reactive oxygen species (ROS) in these arteries which was reduced by calcitriol. Immunofluorescence showed that calcitriol treatment reduced the expression of AT(1)R, NOX-2, NOX-4, and p67(phox) and increased that of superoxide dismutase (SOD)-1. Twelve-hour exposure to calcitriol prevented angiotensin (Ang) II-induced increases in ROS and the over-expression of NOX-2, NOX-4, and p67(phox) in renal arteries from normotensive patients. A specific antagonist of the human vitamin D receptor (VDR), TEI-9647, abolished these effects of calcitriol. Both in vitro exposure to and chronic in vivo administration of calcitriol enhanced relaxations to acetylcholine and abolished exaggerated endothelium-dependent contractions in renal arteries of normotensive rats pre-exposed to Ang II or harvested from spontaneously hypertensive rats (SHR). Reactive oxygen species levels and expressions of AT(1)R, NAD(P)H oxidase subunits, SOD-1, and SOD-2 in SHR arteries were normalized by the chronic treatment with calcitriol.
  
  
  CONCLUSIONS
  In vivo and in vitro activation of VDR with calcitriol improves endothelial function by normalizing the expressions of AT(1)R and radical generating and scavenging enzymes and thus preventing ROS over-production. The present findings suggest that calcitriol is effective in preserving endothelial function in hypertension.
authors.affiliation: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Dong
authors.forename: Siu Ling
authors.initials: SL
authors.lastname: Wong
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Hung Kay
authors.initials: HK
authors.lastname: Lee
authors.forename: Chi Fai
authors.initials: CF
authors.lastname: Ng
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Zhen Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; C400545:TEI 9647; D014815:Vitamins; D003609:Dactinomycin; D010088:Oxidoreductases; D002117:Calcitriol