Effects of simvastatin and pravastatin on endothelium-dependent relaxation in hypercholesterolemic rabbits.

OBJECTIVES: The present study was conducted to investigate endothelium-dependent relaxation in hypercholesterolemic rabbits after treatment with two HMG-CoA reductase inhibitors: Simvastatin and Pravastatin. METHODS: Thirty male New Zealand rabbits were randomly assigned to Control, Simvastatin and Pravastatin groups and fed a diet supplemented with lipids and cholesterol (coconut oil 10% and cholesterol 1%) for 8 weeks. The drugs were administered in dosages of 10 mg/kg from the fourth to seventh weeks; at the end of the seventh week, plasma cholesterol was determined, and the Pravastatin dosage adjusted to 15 mg/kg to obtain similar levels of plasma cholesterol for the two experimental groups. At the end of the 8th week, the animals were killed and aorta removed for histologic examination and the measurement of cholesterol content, as well as for the conduction of endothelium-dependent relaxation studies. RESULTS: At the end of the study serum cholesterol was reduced by 57.1% in the Pravastatin group and 58.4% in the Simvastatin group, with the aortic cholesterol content in the former being significantly lower than that of the Simvastatin and Control groups (p < 0.05). Histologic examination also revealed a significant decrease in volume fractions of foam cells in Pravastatin-treated animals, whereas endothelium-dependent relaxation in response to ACh was significantly impaired in the Simvastatin group. No significant difference was found in relaxation induced by nitroprusside. CONCLUSIONS: In spite of the similar reduction in plasma cholesterol obtained by different doses, it seems that Pravastatin preserves the endothelium-dependent relaxation of aortic rings of hypercholesterolemic rabbits more effectively than does Simvastatin.