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Nitric oxide-sensitive guanylyl cyclase signaling affects CO 2 -dependent but not pressure-dependent regulation of cerebral blood flow.

Authors :
Jahshan S
Dayan L
Jacob G
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.)

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