Purpose
Previous studies have demonstrated neuronal protective effects of statin treatment. ADMA is an inhibitor of endogenous nitric oxide, which regulates blood circulation to adjust vascular diameter, and is considered to inversely correlated with nitric oxide production. The objective of the present study was to determine whether atorvastatin treatment to SHRSPs protects against stroke. Serum biochemical examinations including ADMA were also examined.
Methods
Male 8 weeks SHRSPs were treated orally daily with atorvastatin suspension at a high dose of 20 mg/kg (n=10, A group) or a low dose of 2 mg/kg (n=10, B group). Vehicle male 8 weeks SHRSPs were treated orally daily with same amount of suspension without atorvastatin (n=10, V group). Body weight was measured every day after treatment started, and blood pressure and heart rate were measured at the age of 8 and 17 weeks. To determine a morbidity of stroke, neurological score was examined every day. Biochemical examinations including cholesterol and ADMA were measured at the age of 19 weeks.
Results
Each mean survival times were 76 (A group), 64 (B group) and 50 (V group) days from the day of treatment started (Kaplan-Meier method). Survival period in A group was significant longer than that in V group (logrank test). Each mean period of stroke morbidity were 42 (A group), 39 (B group) and 35 (V group) days from the day of treatment started (Kaplan-Meier method). The period of stroke morbidity in A group was significant longer than that in V group (loglank test). There were no significant differences in body weight, blood pressure and heart rate among three groups (Dunnet test). ADMA was significantly lower in A group (0.61±0.06) than V group (0.81±0.18) (mean±SD, Dunett multiple comparison test), whereas there were no significant differences in biochemical examinations of serum cholesterol, renal and liver functions and creatinine phosphokinase.
Conclusions
It was demonstrated that atorvastatin treatment reduced morbidity and mortality of stroke in SHRSPs. It was suggested that this protection was mediated by up regulation of nitric oxide production by atorvastatin treatment.