Atorvastatin prevented and partially reversed adrenocorticotropic hormone-induced hypertension in the rat.
1. 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 cent < 0.01). Ato partially reversed ACTH-induced hypertension (124 +/- 3 and 136 +/- 2 mmHg, respectively, P cent < 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 micromol/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.
Mondo
Charles K
CK
Institute of Cardiology, 2nd Hospital, Tianjin Medical University, Tianjin city, PR China. cmondo@excite.com
Yang
Wan-Song
WS
Su
Ji-Zhou
JZ
Huang
Ti-Gang
TG
D000324:Adrenocorticotropic Hormone; D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013481:Superoxides; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D000069059:Atorvastatin