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(Circulation. 2003;107:1901.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Role of Nitric Oxide in the Regulation of Cerebral Blood Flow in Humans

Chemoregulation Versus Mechanoregulation

From the J. Recanati Autonomic Dysfunction Center (S.L., R.E., G.J.), Departments of Cardiology (S.L.) and Anesthesiology (R.L.), Rambam Medical Center, and Technion-Israel Institute of Technology, Haifa, Israel.

Correspondence to Giris Jacob, MD, DSc, Jacob Recanati Autonomic Dysfunction Center, Medicine A, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel. E-mail G_Jacob{at}rambam.health.gov.il

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.

Methods and 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 · s^-1; P=0.01, resulting in unaffected CBF. Phenylephrine (25 to 250 µg) 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 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.

Key Words: nitric oxide • receptors, adrenergic, alpha • cerebrovascular disorders • cerebrovascular circulation

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