The effect of sildenafil on nitric oxide-mediated vasodilation in healthy men
Abstract
BACKGROUND: Sildenafil, a treatment for erectile dysfunction, is a specific phosphodiesterase type 5 (PDE 5) inhibitor that enhances nitric oxide (NO)-mediated vasodilation in the corpus cavernosum by inhibiting cyclic guanosine monophosphate breakdown. Since PDE 5 is widely expressed in the vasculature, we examined the hypothesis that sildenafil could enhance NO-mediated vasodilation in other vascular beds and improve endothelial function.
METHODS: NO-mediated responses to acetylcholine (endothelium-dependent) and nitroglycerin (endothelium-independent) were measured in healthy men in the dorsal hand vein (n = 13), after the administration of either sildenafil 50 mg or placebo. Flow-mediated dilation of the brachial artery and forearm postischemic reactive hyperemia were measured before and after sildenafil 50 mg, isosorbide dinitrate 5 mg, and placebo in a double-blind, randomized, crossover study (n = 11).
RESULTS: In the hand vein, sildenafil administration increased sensitivity to local nitroglycerin. The 50% effective dose decreased approximately 4-fold from 13.5 ng/min (range, 6.9-26.6 ng/min) to 2.7 ng/min (range, 1.1-6.4 ng/min) (P =.025). Sildenafil decreased the maximum venoconstriction induced by phenylephrine from 81% +/- 3% to 74% +/- 3% (P =.025). Sildenafil did not significantly affect the maximal venodilatory response to acetylcholine (35% +/- 7% after placebo versus 32% +/- 8% after sildenafil) (P =.7). In the arterial vasculature, flow-mediated dilation…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 13 participants or records.
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