TY - JOUR
T1 - Sympathetic activation by sildenafil
AU - Phillips, Bradley G.
AU - Kato, Masahiko
AU - Pesek, Catherine A.
AU - Winnicki, Mikolaj
AU - Narkiewicz, Krzysztof
AU - Davison, Diane
AU - Somers, Virend K.
PY - 2000/12/19
Y1 - 2000/12/19
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Heart rate
KW - Nervous system, sympathetic
KW - Sildenafil citrate
KW - Stress
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U2 - 10.1161/01.CIR.102.25.3068
DO - 10.1161/01.CIR.102.25.3068
M3 - Article
C2 - 11120696
AN - SCOPUS:0034687588
SN - 0009-7322
VL - 102
SP - 3068
EP - 3073
JO - Circulation
JF - Circulation
IS - 25
ER -