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.
RCT Entities:
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: Jacqueline K Limberg; Katherine R Malterer; J Mikhail Kellawan; William G Schrage; Brad W Wilkins; Wayne T Nicholson; John H Eisenach; Michael J Joyner; Timothy B Curry Journal: Eur J Appl Physiol Date: 2016-12-24 Impact factor: 3.078
Authors: T Radovits; T Bömicke; G Kökény; R Arif; S Loganathan; K Kécsán; S Korkmaz; E Barnucz; P Sandner; M Karck; G Szabó Journal: Br J Pharmacol Date: 2009-03-04 Impact factor: 8.739
Authors: A Schäfer; D Fraccarollo; S Pförtsch; U Flierl; C Vogt; J Pfrang; A Kobsar; T Renné; M Eigenthaler; G Ertl; J Bauersachs Journal: Br J Pharmacol Date: 2007-09-24 Impact factor: 8.739
Authors: Alin Stirban; Simona Nandrean; Stanley Kirana; Christian Götting; Ioan Andrei Veresiu; Diethelm Tschoepe Journal: Int J Vasc Med Date: 2012-10-03