BACKGROUND:Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS: We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP-mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS: Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (-73% ± 3% vs -63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS:Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic-mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the significant hypotension observed in patients taking alpha-blockers with sildenafil.
RCT Entities:
BACKGROUND:Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS: We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP-mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS: Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (-73% ± 3% vs -63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS:Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic-mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the significant hypotension observed in patients taking alpha-blockers with sildenafil.
Authors: James E Faber; Caroline L Szymeczek; Susanna Cotecchia; Steven A Thomas; Akito Tanoue; Gozoh Tsujimoto; Hua Zhang Journal: Am J Physiol Heart Circ Physiol Date: 2007-01-12 Impact factor: 4.733
Authors: Raymond C Rosen; John T Wei; Stanley E Althof; Allen D Seftel; Martin Miner; Michael A Perelman Journal: Urology Date: 2009-01-23 Impact factor: 2.649
Authors: Rubens Fazan; Domitila A Huber; Carlos Alberto A Silva; Valdo J Dias da Silva; Maria Cristina O Salgado; Helio C Salgado Journal: J Appl Physiol (1985) Date: 2008-04-03
Authors: Delphine Behr-Roussel; Alexandra Oudot; Stéphanie Caisey; Olivier L E Coz; Diane Gorny; Jacques Bernabé; Chris Wayman; Laurent Alexandre; François A Giuliano Journal: Eur Urol Date: 2007-11-20 Impact factor: 20.096
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: J Mikhail Kellawan; Jacqueline K Limberg; Zachariah M Scruggs; Wayne T Nicholson; William G Schrage; Michael J Joyner; Timothy B Curry Journal: J Appl Physiol (1985) Date: 2017-10-05
Authors: Clênia de Oliveira Cavalcanti; Rafael R Alves; Alessandro L de Oliveira; Josiane de Campos Cruz; Maria do Socorro de França-Silva; Valdir de Andrade Braga; Camille de Moura Balarini Journal: Front Physiol Date: 2016-01-28 Impact factor: 4.566
Authors: Ananda T Dias; Amanda S Cintra; Jéssica C Frossard; Zaira Palomino; Dulce E Casarini; Isabele B S Gomes; Camille M Balarini; Agata L Gava; Bianca P Campagnaro; Thiago M C Pereira; Silvana S Meyrelles; Elisardo C Vasquez Journal: J Transl Med Date: 2014-09-16 Impact factor: 5.531