Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction.
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.
Vlachopoulos
Charalambos
C
Cardiovascular and Sexual Health Unit, First Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece. cvlachop@otenet.gr
Tsekoura
Dorothea
D
Alexopoulos
Nikolaos
N
Panagiotakos
Demosthenes
D
Aznaouridis
Konstantinos
K
Stefanadis
Christodoulos
C
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
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate