Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes

Abstract

OBJECTIVE—Flow-mediated dilatation (FMD), induced by occlusion of the brachial artery, is an index of nitric oxide-dependent endothelial function that is impaired in patients with type 2 diabetes. Sildenafil (Viagra) is an inhibitor of phosphodiesterase 5 (PDE-5), which is used for management of erectile dysfunction in a broad range of patients, including those with type 2 diabetes. Its effects on endothelial function in these patients have not been previously assessed. RESEARCH DESIGN AND METHODS—We assessed the acute and prolonged effects of a low dose of sildenafil (25 mg) on FMD in patients with type 2 diabetes. We performed a double-blind, placebo-controlled cross-over trial in 16 patients (14 of whom completed the study) with type 2 diabetes who had erectile dysfunction without overt clinical heart disease. RESULTS—In these patients, the mean ± SD brachial artery diameter (BAD) measured by ultrasound was 4.33 ± 0.6 mm. After inducing FMD, the BAD increased 8% to 4.66 ± 0.6 mm (P = 0.2). One hour after oral administration of sildenafil 25 mg, FMD increased the BAD significantly by 15% to 4.99 ± 0.5 mm (P ≤ 0.01), whereas it did not change with placebo (4.6 ± 0.6 mm, P = 0.1). After treatment with sildenafil 25 mg daily for 2 weeks and testing 24 h after the last dose, the mean FMD was 14% (P = 0.01). In contrast, the mean FMD with placebo was 9% (P = 0.45). CONCLUSIONS—We conclude that acute and prolonged sildenafil treatment has a favorable effect on brachial artery flow-mediated dilatation that persists for at least 24 h after the last dose. Further investigation is needed to determine whether this prolonged effect has clinical implications in patients with type 2 diabetes.