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ANTI‐OXIDANT EFFECTS OF ATORVASTATIN IN DEXAMETHASONE‐INDUCED HYPERTENSION IN THE RAT
Author(s) -
Mondo Charles K,
Yang WanSong,
Zhang Nan,
Huang TiGang
Publication year - 2006
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2006.04482.x
Subject(s) - enos , atorvastatin , endocrinology , medicine , dexamethasone , endothelial dysfunction , blood pressure , nitric oxide , phenylephrine , vasoconstriction , nitric oxide synthase , chemistry
SUMMARY1 Dexamethasone (Dex)‐induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide () production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced 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 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 µg/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.