Sympathetic activation by sildenafil.
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.


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.
Phillips
B G
BG
Division of Clinical and Administrative Pharmacy, Department of Internal Medicine, University of Iowa, Iowa City, USA.
Kato
M
M
Pesek
C A
CA
Winnicki
M
M
Narkiewicz
K
K
Davison
D
D
Somers
V K
VK
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D012146:Rest; D000068677:Sildenafil Citrate; D013312:Stress, Physiological / Q000503:physiopathology; D013450:Sulfones; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human