title: Nitric oxide synthesis couples cerebral blood flow and metabolism.
abstract: The most fundamental aspect of the cerebral circulation is the well-described coupling of cerebral metabolic activity and cerebral blood flow. A number of substances have been proposed to link flow and metabolism, including K+, pH and adenosine. In the alpha-chloralose anaesthetised cat we studied simultaneously cerebral neuronal activity and local blood flow to attempt to dissociate the two and thus determine the coupling substance. Neuronal activity was determined by monitoring unit firing in the parietal cortex with tungsten in glass microelectrodes while local cerebral blood flow in the same area was monitored continuously using laser Doppler flowmetry. To initiate an increase in metabolic activity and, pari passu, blood flow spreading depression was elicited by needle stick injury. Spreading depression when initiated causes a wave of depolarization, measured as an increased firing rate and associated marked (400 +/- 95%) increase in local cerebral blood flow. Intravenous administration of NG-nitro-L-arginine methyl ester (1-NAME), a potent nitric oxide synthase inhibitor, produced a complete blockade of the hyperemia associated with spreading depression but no change in either resting cell firing or spreading depression-evoked increases in firing rate. These data demonstrate at least for spreading depression-elicited increases in metabolic activity, that nitric oxide (NO) is a key coupling compound that links changes in cerebral blood flow and metabolism. These data imply that NO may have a more general role in flow/metabolism coupling and further studies in other situations are required to determine the extent to which NO is responsible for this fundamental cerebrovascular phenomenon.
authors: Department of Neurology, Prince Henry Hospital, Sydney, NSW, Australia.
authors: P J
authors: PJ
authors: Goadsby
authors: H
authors: H
authors: Kaube
authors: K L
authors: KL
authors: Hoskin
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004594:Electrophysiology; D017078:Laser-Doppler Flowmetry; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester