title: Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases.
abstract: Cerebral blood flow (CBF) is highly regulated by changes in arterial Pco(2) and arterial Po(2). Evidence from animal studies indicates that various vasoactive factors, including release of norepinephrine, endothelin, adrenomedullin, C-natriuretic peptide (CNP), and nitric oxide (NO), may play a role in arterial blood gas-induced alterations in CBF. For the first time, we directly quantified exchange of these vasoactive factors across the human brain. Using the Fick principle and transcranial Doppler ultrasonography, we measured CBF in 12 healthy humans at rest and during hypercapnia (4 and 8% CO(2)), hypocapnia (voluntary hyperventilation), and hypoxia (12 and 10% O(2)). At each level, blood was sampled simultaneously from the internal jugular vein and radial artery. With the exception of CNP and NO, the simultaneous quantification of norepinephrine, endothelin, or adrenomedullin showed no cerebral uptake or release during changes in arterial blood gases. Hypercapnia, but not hypocapnia, increased CBF and caused a net cerebral release of nitrite (a marker of NO), which was reflected by an increase in the venous-arterial difference for nitrite: 57 +/- 18 and 150 +/- 36 micromol/l at 4% and 8% CO(2), respectively (both P < 0.05). Release of cerebral CNP was also observed during changes in CO(2) (hypercapnia vs. hypocapnia, P < 0.05). During hypoxia, there was a net cerebral uptake of nitrite, which was reflected by a decreased venous-arterial difference for nitrite: -96 +/- 14 micromol/l at 10% O(2) (P < 0.05). These data indicate that there is a differential exchange of NO across the brain during hypercapnia and hypoxia and that CNP may play a complementary role in CO(2)-induced CBF changes.
authors.affiliation: Department of Physiology, University of Otago, Dunedin, New Zealand.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Peebles
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Leo
authors.initials: L
authors.lastname: Celi
authors.forename: Ken
authors.initials: K
authors.lastname: McGrattan
authors.forename: Carissa J
authors.initials: CJ
authors.lastname: Murrell
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply*; D002245:Carbon Dioxide / Q000097:blood*; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology; D002550:Cerebral Veins / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D016857:Hypocapnia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008955:Models, Cardiovascular; D020098:Natriuretic Peptide, C-Type / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D010100:Oxygen / Q000097:blood*; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D020098:Natriuretic Peptide, C-Type; D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen