(Circulation. 2000;102:3068.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Sympathetic Activation by Sildenafil
From the Division of Clinical and Administrative Pharmacy (B.G.P., M.K.) and the Department of Internal Medicine (C.A.P.), University of Iowa, Iowa City; the Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland (K.N.); and the Divisions of Hypertension and Cardiovascular Diseases, Mayo Clinic, Rochester, Minn (M.W., D.D., V.K.S.).
Correspondence to Virend K. Somers, MD, PhD, Divisions of Hypertension and Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail somers.virend{at}mayo.edu
Background—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.
Methods and Results—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<0.05).
Conclusions—Sildenafil causes a marked increase in sympathetic activation, evident both at rest and during stressful stimuli. Sympathetic activation by sildenafil may have implications for understanding cardiovascular events associated with sildenafil use.
Key Words: sildenafil citrate • blood pressure • heart rate • nervous system, sympathetic • stress
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