Sympathetic activation by sildenafil

• Published in: Circulation (New York, N.Y.) N.Y.), 2000-12, Vol.102 (25), p.3068-3073
• Main Authors: PHILLIPS, Bradley G, KATO, Masahiko, PESEK, Catherine A, WINNICKI, Mikolaj, NARKIEWICZ, Krzysztof, DAVISON, Diane, SOMERS, Virend K
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Central Venous Pressure - drug effects; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Heart Rate - drug effects; Hemodynamics - drug effects; Humans; Lower Body Negative Pressure; Male; Medical sciences; Muscle, Skeletal - innervation; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - metabolism; Piperazines - pharmacology; Purines; Rest; Sildenafil Citrate; Stress, Physiological - physiopathology; Sulfones; Sympathetic Nervous System - drug effects; Vasodilator Agents - pharmacology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.102.25.3068

Sildenafil citrate is an effective and widely prescribed therapy for erectile dysfunction. Little is known about the effects of sildenafil on neural control of the circulation or about the effects of sildenafil on neurocirculatory stress responses. We studied 14 normal volunteers (age 32+/-7 years) who were randomized in a double-blind crossover fashion to receive a single oral dose of sildenafil 100 mg or placebo on 2 separate study days. Blood pressure, heart rate, forearm vascular resistance, muscle sympathetic nerve activity, and plasma catecholamines were measured at baseline and at 30 and 60 minutes after sildenafil and after placebo administration. The effects of sildenafil and placebo on neural and circulatory responses to stressful stimuli (sustained handgrip, maximal forearm ischemia, mental stress, and the cold pressor test) were also evaluated. Blood pressure, heart rate, and forearm vascular resistance after sildenafil and placebo were similar. However, muscle sympathetic nerve activity increased strikingly after sildenafil (by 141+/-26%, mean+/-SEM) compared with placebo (3+/-8%) (P=0.006); plasma norepinephrine levels also increased by 31+/-5% after sildenafil administration (P=0.004). Sympathetic nerve traffic during mental, physical, and cold stresses was 2- to 8-fold higher after sildenafil than with placebo (P