Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes

Objective Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). Methods In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. Results After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 +/- 0.5 to 12.5 +/- 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. Conclusions In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition.