title: Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction.
abstract: BACKGROUND
  Endothelial dysfunction is a key early event in the process of atherosclerosis and a risk factor for cardiovascular events. Sildenafil, an effective oral treatment for patients with erectile dysfunction, inhibits cGMP degradation by specific type 5 phosphodiesterase (PDE) inhibition. Sildenafil has been shown to improve vascular function, however, the effect of type 5 PDE inhibition on acute smoking-induced endothelial dysfunction is unknown.
  
  
  METHODS
  We studied the effect of 50 mg of sildenafil on acute smoking-induced endothelial dysfunction in 14 male smokers according to a randomized, placebo-controlled, cross-over design. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasonography.
  
  
  RESULTS
  Sildenafil abolishes the decrease in FMD of the brachial artery that is induced acutely by smoking (placebo/smoking session: from 4.56% +/- 0.60% to 2.80% +/- 0.43%, sildenafil/smoking session: from 3.83% +/- 0.64% to 4.33% +/- 0.47%, ie, improvement of 51%, P < .05). This was associated with no reversal effect of sildenafil on smoking-induced decrease in resting brachial artery diameter and with a partial reversal of the smoking-induced decrease in hyperemic brachial artery diameter (placebo/smoking session: from 4.68 +/- 0.13 mm to 4.53 +/- 0.15 mm, sildenafil/smoking session: from 4.72 +/- 0.12 mm to 4.64 +/- 0.13 mm, ie, improvement of 1.5%, P < .005).
  
  
  CONCLUSIONS
  The present study shows, for the first time, that type 5 PDE inhibition with sildenafil abrogates the smoking-induced acute decrease in FMD of the brachial artery. These findings may have clinical implications given the detrimental consequences of smoking and the strategic role of normal endothelial function.
authors.affiliation: Cardiovascular and Sexual Health Unit, First Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece. cvlachop@otenet.gr
authors.forename: Charalambos
authors.initials: C
authors.lastname: Vlachopoulos
authors.forename: Dorothea
authors.initials: D
authors.lastname: Tsekoura
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Alexopoulos
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Panagiotakos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Aznaouridis
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000208:Acute Disease; D000328:Adult; D018592:Cross-Over Studies; D004108:Dilatation, Pathologic / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines; D000068677:Sildenafil Citrate; D012907:Smoking / Q000009:adverse effects*; D013450:Sulfones; D014652:Vascular Diseases / Q000209:etiology / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate