Sildenafil does not improve nitric oxide-mediated endothelium-dependent vascular responses in smokers

Aims To examine the hypothesis that sildenafil, a phosphodiesterase type 5 inhibitor that inhibits cGMP breakdown, could enhance nitric oxide-mediated vasodilation and reverse endothelial dysfunction in chronic smokers. Methods Flow-mediated dilation of the brachial artery and forearm postischemic reactive hyperemia (both nitric oxide-mediated responses) were measured before and after sildenafil 50 mg and placebo in a double-blind, randomized, crossover study in 9 men who were chronic smokers (21+/-3 pack years). Results There was no significant change in flow-mediated dilation after either sildenafil (0.18%, 95% CI -1.7-2%) or placebo (0.24%, 95% CI -2.8-3.3%) (P=0.88 and 0.8, respectively). Sildenafil had no significant effect on resting forearm blood flow or postischemic reactive hyperemia (P=0.39 and 0.7, respectively). Resting heart rate and blood pressure were unaffected by sildenafil. Conclusions Acute sildenafil administration did not improve endothelial function in chronic smoking men.