Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs

1 Division of Pediatric Cardiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032; Departments of 2 Physiology and 3 Pathology, New York Medical College, Valhalla, New York 10595; 4 Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520; and 5 Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts 02115 Statin drugs can upregulate endothelial nitric oxide (NO) synthase (eNOS) in isolated endothelial cells independent of lipid-lowering effects. We investigated the effect of short-term simvastatin administration on coronary vascular eNOS and NO production in conscious dogs and canine tissues. Mongrel dogs were instrumented under general anesthesia to measure coronary blood flow (CBF). Simvastatin (20 mg · kg 1 · day 1 ) was administered orally for 2 wk; afterward, resting CBF was found to be higher compared with control ( P