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 μg/kg/m in and 1.1 μg/kg/min were studied in 3 groups of baboons. The flow was measured by the in-tracarotid ¹³⁹xenon 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 extraneuronal COMT enzyme is important in limiting the access of blood-borne NE to cerebrovascular constrictor receptors.