Cerebral haemodynamic response or excitability is not affected by sildenafil

TY - JOUR

T1 - Cerebral haemodynamic response or excitability is not affected by sildenafil

AU - Kruuse, Christina

AU - Hansen, Adam E

AU - Larsson, Henrik B W

AU - Lauritzen, Martin

AU - Rostrup, Egill

PY - 2009/4

Y1 - 2009/4

N2 - Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70.3+/-6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.

AB - Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70.3+/-6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.

KW - Adult

KW - Cerebrovascular Circulation/drug effects

KW - Evoked Potentials, Visual

KW - Female

KW - Headache/chemically induced

KW - Hemodynamics/drug effects

KW - Humans

KW - Hypercapnia

KW - Magnetic Resonance Imaging

KW - Photic Stimulation

KW - Piperazines/adverse effects

KW - Purines/adverse effects

KW - Sildenafil Citrate

KW - Sulfones/adverse effects

KW - Young Adult

U2 - 10.1038/jcbfm.2009.10

DO - 10.1038/jcbfm.2009.10

M3 - Journal article

C2 - 19209179

SN - 0271-678X

VL - 29

SP - 830

EP - 839

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 4

ER -