title: Release of noradrenaline into the cerebrovascular circulation in patients with primary hypertension.
abstract: The conventional view is that a 'blood-brain barrier' prevents the passage into the bloodstream of noradrenaline released as a transmitter in the brain. When we tested directly for noradrenaline spillover, sampling via high right and left internal jugular venous catheters in 22 untreated patients with primary hypertension, release of noradrenaline into the cerebrovascular circulation was detected. The concentration of noradrenaline was 14.8% (mean 0.29 nmol/l) higher in right jugular venous than arterial plasma, and 29.8% (mean 0.55 nmol/l) higher in left (both P less than 0.02, Student's paired t-test). Asymmetry in the cerebral venous drainage pattern (right jugular typically largely represents cortical flow, left jugular subcortical flow) and flow rate (usually lower on the left) may underlie the higher venoarterial plasma concentration gradient on the left. Cerebral noradrenaline overflow was calculated from the cerebral plasma flow, the venoarterial noradrenaline plasma concentration gradient across the brain and transcerebral extraction of radiolabelled noradrenaline. Mean cerebral noradrenaline spillover was 220 pmol/min, accounting for 9.1% of total noradrenaline release to plasma (determined by isotope dilution). Since the ganglionic blocker arfonad reduced whole-body noradrenaline spillover (principally derived from sympathetic nerves), but not cerebral spillover, the noradrenaline overflow appears to originate from brain neurones and not cerebrovascular sympathetic nerves. Jugular venous noradrenaline measurements may provide a direct 'window' into noradrenergic brain mechanisms in primary hypertension, with bilateral sampling perhaps allowing differentiation of cortical from subcortical neurotransmitter function.
authors.affiliation: Baker Medical Research Institute, Alfred Hospital, Melbourne, Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Esler
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: G W
authors.initials: GW
authors.lastname: Lambert
mesh_terms: D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D005260:Female; D006973:Hypertension / Q000097:blood*; D008297:Male; D009638:Norepinephrine / Q000097:blood*
chemical_list: D009638:Norepinephrine