Role of catecholamine degradative enzymes and the adrenergic innervation in determining the cerebrovascular response to infused norepinephrine.
Cerebral blood flow responses to intra-arterial infusion of norepinephrine (NE) at 0.55 microgram/kg/min and 1.1 microgram/kg/min were studied in 3 groups of baboons. The flow was measured by the intracarotid 133xenon clearance technique using a computer program to calculate flow (height over area--H/A) flow (initial slope--is) and cerebral metabolic utilization of oxygen (CMRO2). The normal response to NE was to increase flow without significant changes in CMRO2. Blockade of catechol-o-methyl transferase (COMT) produced vasoconstrictor responses to these same NE doses. Monoamine oxidase blockade abolished the normal vasodilation. Denervation of the cerebral circulation with intracisternal 6-hydroxydopamine produced vasoconstrictor responses with flow (H/A) but not with flow (is). It is concluded that the extra-neuronal COMT enzyme is important in limiting the access of blood-borne NE to cerebrovascular constrictor receptors.
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000502:physiology*; D065098:Catechol O-Methyltransferase Inhibitors; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003714:Denervation; D000882:Haplorhini; D006892:Hydroxydopamines / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010215:Papio; D014980:Xenon Radioisotopes
D065098:Catechol O-Methyltransferase Inhibitors; D006892:Hydroxydopamines; D008996:Monoamine Oxidase Inhibitors; D014980:Xenon Radioisotopes; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D009638:Norepinephrine