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Nitric oxide-sensitive guanylyl cyclase signaling affects CO 2 -dependent but not pressure-dependent regulation of cerebral blood flow.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2017 Jun 01; Vol. 312 (6), pp. R948-R955. Date of Electronic Publication: 2017 Mar 29. - Publication Year :
- 2017
-
Abstract
- Cerebrovascular CO <subscript>2</subscript> reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO <subscript>2</subscript> reactivity. 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 CO <subscript>2</subscript> (EtCO <subscript>2</subscript> ) were assessed at baseline (CO <subscript>2</subscript> ~39 mmHg), during hyperventilation (CO <subscript>2</subscript> ~24 mmHg), during hypercapnia (CO <subscript>2</subscript> ~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 EtCO <subscript>2</subscript> : 117 ± 2/67 ± 3 mmHg, 69 ± 3 beats/min, 84 ± 5 and 57 ± 4 cm/s, 1.56 ± 0.1 mmHg·cm <superscript>-1</superscript> ·s <superscript>-1</superscript> , 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 CO <subscript>2</subscript> reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Adult
Blood Flow Velocity
Blood Pressure
Dose-Response Relationship, Drug
Electrocardiography
Healthy Volunteers
Homeostasis
Humans
Hypercapnia blood
Hypercapnia enzymology
Hypercapnia physiopathology
Hyperventilation blood
Hyperventilation enzymology
Hyperventilation physiopathology
Injections, Intravenous
Male
Middle Cerebral Artery enzymology
Middle Cerebral Artery physiopathology
Phenylephrine administration & dosage
Tilt-Table Test
Time Factors
Ultrasonography, Doppler, Transcranial
Vasoconstriction
Vasoconstrictor Agents administration & dosage
Young Adult
Carbon Dioxide blood
Cerebrovascular Circulation drug effects
Middle Cerebral Artery drug effects
Nitric Oxide metabolism
Phosphodiesterase 5 Inhibitors pharmacology
Signal Transduction drug effects
Sildenafil Citrate pharmacology
Soluble Guanylyl Cyclase metabolism
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 312
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 28356297
- Full Text :
- https://doi.org/10.1152/ajpregu.00241.2016