Sildenafil improves dynamic vascular function in the brain: studies in patients with pulmonary hypertension.
BACKGROUND
Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease.


METHODS
In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers.


RESULTS
Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost.


CONCLUSIONS
Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.
Rosengarten
B
B
Department of Neurology, University Hospital, Justus Liebig University Giessen, Giessen, Germany. bernhard.rosengarten@neuro.med.uni-giessen.de
Schermuly
R T
RT
Voswinckel
R
R
Kohstall
M G
MG
Olschewski
H
H
Weissmann
N
N
Seeger
W
W
Kaps
M
M
Grimminger
F
F
Ghofrani
H A
HA
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020769:Posterior Cerebral Artery / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000502:physiology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D017585:Ultrasonography, Doppler, Transcranial; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D016285:Iloprost