title: Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.
abstract: 1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.
authors.affiliation: Institute of Cardiology, 2nd Hospital, Tianjin Medical University, Tianjin, China. charles_mondo@yahoo.com.au
authors.forename: Charles K
authors.initials: CK
authors.lastname: Mondo
authors.forename: Wan-Song
authors.initials: WS
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Ti-Gang
authors.initials: TG
authors.lastname: Huang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001011:Aorta / Q000201:enzymology; D000069059:Atorvastatin; D003907:Dexamethasone / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D003907:Dexamethasone; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III