title: Sildenafil does not improve nitric oxide-mediated endothelium-dependent vascular responses in smokers.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Clinical Pharmacology, General Clinical Research Center, Department of Biomedical Engineering, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Dishy
authors.forename: Paul A
authors.initials: PA
authors.lastname: Harris
authors.forename: Rosanna
authors.initials: R
authors.lastname: Pierce
authors.forename: Harish C
authors.initials: HC
authors.lastname: Prasad
authors.forename: Gbenga
authors.initials: G
authors.lastname: Sofowora
authors.forename: Holly L
authors.initials: HL
authors.lastname: Bonar
authors.forename: Alastair J J
authors.initials: AJ
authors.lastname: Wood
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D012907:Smoking / Q000503:physiopathology*; D013450:Sulfones; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate