title: Nitric oxide-sensitive guanylyl cyclase signaling affects CO2-dependent but not pressure-dependent regulation of cerebral blood flow.
abstract: Cerebrovascular CO2reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO2reactivity. Fourteen healthy males (34 ± 2 yr) were enrolled in the study. Blood pressure (BP), ECG, velocity of cerebral blood flow (CBF; measured by transcranial Doppler), and end-tidal CO2(EtCO2) were assessed at baseline (CO2~39 mmHg), during hyperventilation (CO2~24 mmHg), during hypercapnia (CO2~46 mmHg), during boluses of phenylephrine (25-200 µg), and during graded head-up tilting (HUT). Measurements were repeated 1 h after 100 mg sildenafil were taken. Results showed that sildenafil did not affect resting BP, heart rate, CBF peak and mean velocities, estimated regional cerebrovascular resistance (eCVR; mean BP/mean CBF), breath/min, and EtCO2: 117 ± 2/67 ± 3 mmHg, 69 ± 3 beats/min, 84 ± 5 and 57 ± 4 cm/s, 1.56 ± 0.1 mmHg·cm-1·s-1, 14 ± 0.5 breaths/min, and 39 ± 0.9 mmHg, respectively. Sildenafil increased and decreased the hypercapnia induced in CBF and eCVR, respectively. Sildenafil also attenuated the decrease in peak velocity of CBF, 25 ± 2 vs. 20 ± 2% (P< 0.05) and increased the eCVR, 2.5 ± 0.2 vs. 2 ± 0.2% (P< 0.03) during hyperventilation. Sildenafil did not affect CBF despite significant increases in the eCVRs that were elicited by phenylephrine and HUT. This investigation suggests that sildenafil, which potentiates the NO-cGMP signaling, seems to affect the cerebrovascular CO2reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation.
authors.affiliation: J. Recanati Autonomic Dysfunction Center, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel.|Neurosurgery Department, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel; and.
authors.forename: Shadi
authors.initials: S
authors.lastname: Jahshan
authors.affiliation: J. Recanati Autonomic Dysfunction Center, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Dayan
authors.affiliation: Department of Internal Medicine, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel; jacobgi@tlvmc.gov.il.|J. Recanati Autonomic Dysfunction Center, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel.|Faculty of Medicine, Tel Aviv "Sourasky" Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Giris
authors.initials: G
authors.lastname: Jacob
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D064368:Healthy Volunteers; D006706:Homeostasis; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000201:enzymology / Q000503:physiopathology; D006985:Hyperventilation / Q000097:blood / Q000201:enzymology / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000008:administration & dosage; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*; D018667:Tilt-Table Test; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D010656:Phenylephrine; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D000071756:Soluble Guanylyl Cyclase
keywords: CO2 reactivity; PDE5 inhibitor; autoregulation; cerebral blood flow; sildenafil