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ATORVASTATIN PREVENTED AND PARTIALLY REVERSED ADRENOCORTICOTROPIC HORMONE‐INDUCED HYPERTENSION IN THE RAT
Author(s) -
Mondo Charles K,
Yang WanSong,
Su JiZhou,
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.1440-1681.2006.04377.x
Subject(s) - adrenocorticotropic hormone , atorvastatin , saline , medicine , endocrinology , nitric oxide , blood pressure , hormone , chemistry
SUMMARY1 Adrenocorticotropic hormone (ACTH)‐induced hypertension is associated with nitric oxide (NO) deficiency and increased oxidative stress. Atorvastatin (Ato), an HMG‐Co‐enzyme‐A reductase inhibitor has been reported to enhance availability of NO. The aim of the study was to assess whether pretreatment with Ato would prevent the development of ACTH‐induced hypertension and whether established ACTH‐induced hypertension could be reversed with subsequent administration of Ato in rats. 2 Male Sprague‐Dawley rats ( n = 60) were treated with Ato (30 mg/kg per day in drinking water) or tap water for 15 days. ACTH (0.2 mg/kg per day s.c) or saline was started 4 days after Ato treatment or non‐treated rats and continued for 11–13 days (prevention study). In the reversal study, Ato was given on day 8 of ACTH/Saline treatment for 5 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. 3 Adrenocorticotropic hormone treatment increased SBP (110 ± 2–136 ± 2 mmHg, P < 0.001) and aortic superoxide production ( P < 0.001). Ato alone did not alter SBP, but Ato pretreatment prevented ACTH‐induced hypertension compared with that in rats treated with ACTH alone (118 ± 2 and 136 ± 2 mmHg, respectively, P ¢ < 0.01). Ato partially reversed ACTH‐induced hypertension (124 ± 3 and 136 ± 2 mmHg, respectively, P ¢ < 0.05). Plasma nitrate/nitrite (NOx) was decreased in ACTH‐treated rats compared with saline treated rats (6.6 ± 0.4 saline and 4.5 ± 0.5 mmol/L ACTH, P < 0.001). Atorvastatin affected neither plasma NOx nor aortic superoxide production. 4 Atorvastatin prevented and partially reversed ACTH‐induced hypertension in the rat.