title: The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects.
abstract: Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler, and regional cerebral blood flow in the perfusion area of the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and xenon inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasound. Blood pressure and heart rate were recorded repeatedly. Headache responses and tenderness of pericranial muscles were scored verbally. Sildenafil caused no significant changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart rate increased and diastolic blood pressure decreased significantly compared to placebo. Despite the lack of cerebral arterial dilatation, sildenafil caused significantly more headache than placebo. The present results show that sildenafil 100 mg does not dilate cerebral or extracerebral arteries but nevertheless causes headache, which may be attributed to nonvascular mechanisms.
authors.affiliation: Department of Neurology, Glostrop Hospital, University of Copenhagen, Denmark. ckruuse@dadlnet.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Kruuse
authors.forename: Lars Lykke
authors.initials: LL
authors.lastname: Thomsen
authors.forename: Torsten Bjørn
authors.initials: TB
authors.lastname: Jacobsen
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines; D012016:Reference Values; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D010208:Papaverine; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human