Role of nitric oxide in the regulation of cerebral blood flow in humans: chemoregulation versus mechanoregulation.
BACKGROUND
From animal studies it emerged that nitric oxide is important for the modulation of CO2-mediated cerebral blood flow (CBF chemoregulation) but not for the pressor-dependent mechanism (mechanoregulation). This hypothesis was tested in 18 healthy subjects.


RESULTS
Peak velocity (PV), diastolic velocity (DV), and mean velocity (MV) were measured by transcranial Doppler of the middle cerebral artery. Chemoregulation was assessed during normocapnia, hypocapnia, and after inhaled mixture of 95% O2+5% CO2. Mechanoregulation was evaluated by incremental doses of phenylephrine. Measurements were repeated during infusion of sodium nitroprusside (SNP). Regional cerebrovascular resistance (CVR) was calculated as mean blood pressure (BP)/MV. SNP infusion decreased mean BP by 7 mm Hg and CVR decreased from 1.38+/-0.08 to 1.29+/-0.09 mm Hg/cm x s(-1); P=0.01, resulting in unaffected CBF. Phenylephrine (25 to 250 microg) caused a similar increase in BP in a dose-response fashion before and during SNP infusion. Despite the increments in BP and CVR, CBF remained unaffected. During hyperventilation (end-tidal CO2 approximately 24 mm Hg), CVR increased by 75+/-3% and PV and DV decreased by 27+/-2% and 43+/-2%, respectively (P<0.001 for all). SNP infusion blunted the vasoconstrictive effect of hypocapnia; CVR increased only by 57+/-5%, and PV and DV decreased by 23+/-2% and 35+/-3%, respectively, (P<0.05 for all). Similarly, SNP augmented the vasodilatory effect of hypercapnia.


CONCLUSIONS
Exogenous nitric oxide donor affects the basal cerebral vascular tone without affecting the CBF mechanoregulation. However, it selectively affects only the chemoregulatory mechanism (CO2-dependent). Thus, the CO2-NO axis is a cardinal pathway for CBF regulation in humans.
Lavi
Shahar
S
Jacob Recanati Autonomic Dysfunction Center, Medicine A, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel. G_Jacob@rambam.health.gov.il
Egbarya
Rania
R
Lavi
Ronit
R
Jacob
Giris
G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging / Q000503:physiopathology; D016857:Hypocapnia / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D017585:Ultrasonography, Doppler, Transcranial
D000316:Adrenergic alpha-Agonists; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide