Pitavastatin Improves Endothelial Function and Glucose Metabolism in Ovariectomized Mice

Abstract

Estrogen deficiency increases the cardiovascular risks and metabolic dysfunction in postmenopausal women. The potential effects of estrogen are partially related to its direct effects on the vascular wall, stimulating endotheliumderived NO synthesis (eNOS). HMG-CoA reductase inhibitors (statins) may also improve the endothelial function through upregulation of eNOS. In this study, we examined whether the treatment of pitavastatin for a short period (1 week) may improve the endothelial function or glucose metabolism under estrogen deficiency induced by ovariectmy. At 4 weeks after ovariectomy, hyperglycemia and hyperinsulinemia were observed in estrogen deficient mice as assessed by intraperitoneal glucose tolerance test, and endothelial dysfunction was also observed as assessed by the vasodilator response to acetylcholine. At 3 weeks after ovariectomy, we started to administer pitavastatin to ovariectomized mice for 1 week. Although the treatment of pitavastatin for a week did not affect obesity, the treatment of pitavastatin significantly attenutaed hyperglycemia and hyperinsulinemia as well as endothelial dysfunction induced by estrogen deficiency. These results demonstrated that treatment of pitavastatin rapidly improved glucose metabolism and endothelial function under estrogen deficiency. Keywords: Endothelial function, eNOS, estrogen, hyperglycemia, hyperinsulinemia, insulin resistance, IGF-1, menopause, ovariectomy, statins