Published Online
on March 10, 2003

A more recent version of this article appeared on April 15, 2003

This Article Full Text (PDF) All Versions of this Article: 107/14/1901    most recent 01.CIR.0000057973.99140.5Av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lavi, S. Articles by Jacob, G. Search for Related Content PubMed PubMed Citation Articles by Lavi, S. Articles by Jacob, G. Related Collections Brain Circulation and Metabolism

Submitted on October 2, 2002
Revised on December 31, 2002
Accepted on January 7, 2003

Role of Nitric Oxide in the Regulation of Cerebral Blood Flow in Humans. Chemoregulation Versus Mechanoregulation

Shahar Lavi MD, Rania Egbarya MD, Ronit Lavi MD, and Giris Jacob MD, DSc^*

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.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				H. J. C. Ravensbergen and I. S. Sahota Broken sleep: a new chronic intermittent hypoxia model for obstructive sleep apnoea J. Physiol., November 15, 2009; 587(22): 5303 - 5304. [Full Text] [PDF]

				L. Dahl Ejby Jensen, R. Cao, E.-M. Hedlund, I. Soll, J. O. Lundberg, G. Hauptmann, J. F. Steffensen, and Y. Cao Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish PNAS, October 27, 2009; 106(43): 18408 - 18413. [Abstract] [Full Text] [PDF]

				E. Nur, Y.-S. Kim, J. Truijen, E. J. van Beers, S. C. A. T. Davis, D. P. Brandjes, B. J. Biemond, and J. J. van Lieshout Cerebrovascular reserve capacity is impaired in patients with sickle cell disease Blood, October 15, 2009; 114(16): 3473 - 3478. [Abstract] [Full Text] [PDF]

				P. Brassard, T. Seifert, and N. H. Secher Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects? Br. J. Anaesth., June 1, 2009; 102(6): 800 - 805. [Abstract] [Full Text] [PDF]

				R. Zhang, K. Behbehani, and B. D. Levine Dynamic pressure\#8211;flow relationship of the cerebral circulation during acute increase in arterial pressure J. Physiol., June 1, 2009; 587(11): 2567 - 2577. [Abstract] [Full Text] [PDF]

				N. Toda, K. Ayajiki, and T. Okamura Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances Pharmacol. Rev., March 1, 2009; 61(1): 62 - 97. [Abstract] [Full Text] [PDF]

				Y.-S. Kim, E. Nur, E. J. van Beers, J. Truijen, S. C.A.T. Davis, B. J. Biemond, and J. J. van Lieshout Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease Stroke, March 1, 2009; 40(3): 808 - 814. [Abstract] [Full Text] [PDF]

				K. C. Peebles, A. M. Richards, L. Celi, K. McGrattan, C. J. Murrell, and P. N. Ainslie Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases J Appl Physiol, October 1, 2008; 105(4): 1060 - 1068. [Abstract] [Full Text] [PDF]

				R. V. Immink, B.-J. H. van den Born, G. A. van Montfrans, Y.-S. Kim, M. W. Hollmann, and J. J. van Lieshout Cerebral Hemodynamics During Treatment With Sodium Nitroprusside Versus Labetalol in Malignant Hypertension Hypertension, August 1, 2008; 52(2): 236 - 240. [Abstract] [Full Text] [PDF]

				V. E. Claydon, G. Gulli, M. Slessarev, O. Appenzeller, G. Zenebe, A. Gebremedhin, and R. Hainsworth Cerebrovascular Responses to Hypoxia and Hypocapnia in Ethiopian High Altitude Dwellers Stroke, February 1, 2008; 39(2): 336 - 342. [Abstract] [Full Text] [PDF]

				J. M. Murkin Cerebral Autoregulation: The Role of CO2 in Metabolic Homeostasis Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2007; 11(4): 269 - 273. [Abstract] [PDF]

				P. N. Ainslie, C. Murrell, K. Peebles, M. Swart, M. A. Skinner, M. J. A. Williams, and R. D. Taylor Early morning impairment in cerebral autoregulation and cerebrovascular CO2 reactivity in healthy humans: relation to endothelial function Exp Physiol, July 1, 2007; 92(4): 769 - 777. [Abstract] [Full Text] [PDF]

				S. Lavi, D. Gaitini, V. Milloul, and G. Jacob Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1856 - H1861. [Abstract] [Full Text] [PDF]

				C. H. E. Imray, S. D. Myers, K. T. S. Pattinson, A. R. Bradwell, C. W. Chan, S. Harris, P. Collins, A. D. Wright, and the Birmingham Medical Research Expeditionary Soci Effect of exercise on cerebral perfusion in humans at high altitude J Appl Physiol, August 1, 2005; 99(2): 699 - 706. [Abstract] [Full Text] [PDF]

				L. J Norcliffe, M Rivera-Ch, V. E Claydon, J. P Moore, F Leon-Velarde, O Appenzeller, and R Hainsworth Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers J. Physiol., July 1, 2005; 566(1): 287 - 294. [Abstract] [Full Text] [PDF]

				R. V. Immink, B.-J. H. van den Born, G. A. van Montfrans, R. P. Koopmans, J. M. Karemaker, and J. J. van Lieshout Impaired Cerebral Autoregulation in Patients With Malignant Hypertension Circulation, October 12, 2004; 110(15): 2241 - 2245. [Abstract] [Full Text] [PDF]