Post-stroke atorvastatin treatment reduces neurological deficits and mortality rate in the stroke-prone spontaneously hypertensive rat.
Several large clinical trials have demonstrated that 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors decreased the incidence of stroke independently of their cholesterol-lowering effect. We have investigated the effect of post-stroke treatment with atorvastatin on neurological deficits and mortality in stroke-prone spontaneously hypertensive rats (SHR-SP). The vehicle-treated group showed significantly aggravated neurological deficits compared with those observed on the first day of stroke. In contrast, the post-stroke oral administration of atorvastatin at 3 or 30 mg kg(-1)/day significantly ameliorated these neurological deficits. Atorvastatin improved the survival rate in a dose-dependent manner, with this effect being significant at 30 mg kg(-1)/day. Atorvastatin did not affect blood pressure, heart rate or total cholesterol in SHR-SP at either dose. In contrast, it significantly increased plasma nitric oxide (NO) levels at both doses. These results indicated that post-stroke administration of atorvastatin ameliorated neurological deficits and prolonged survival, which might have resulted from increased plasma NO, apart from its effect on cholesterol level and blood pressure in SHR-SP. In conclusion, this study demonstrated the protective effects of post-stroke administration of atorvastatin against stroke in SHR-SP.
Hayashi
Aska
A
Applied Pharmacology Research, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. hayashi.asuka@yamanouchi.co.jp
Suzuki
Masanori
M
Ogawa
Yumiko
Y
Sonoda
Rie
R
Sasamata
Masao
M
D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D009569:Nitric Oxide; D002784:Cholesterol; D000069059:Atorvastatin