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 ora
l dose of sildenafil 100 mg or placebo on 2 separate study days. Blood pres
sure, heart rate, forearm vascular resistance, muscle sympathetic nerve act
ivity, 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 sti
muli (sustained handgrip, maximal forearm ischemia, mental stress, and the
cold presser test) were also evaluated. Blood pressure, heart rate, and for
earm 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 administra
tion (P=0.004)I Sympathetic nerve traffic during mental, physical, and cold
stresses was 2- to 8-fold higher after sildenafil than with placebo (P<0.0
5).
Conclusions-Sildenafil causes a marked increase in sympathetic activation,
evident both at rest and during stressful stimuli. Sympathetic activation b
y sildenafil may have implications for understanding cardiovascular events
associated with sildenafil use.