Increased norepinephrine spillover into the jugular veins in essential hypertension.
In essential hypertension sympathetic nerve firing is commonly increased. A central nervous system origin has been presumed but not tested directly. To estimate cerebral norepinephrine release in essential hypertension, spillover of norepinephrine into the cerebrovascular circulation was measured by isotope dilution, with high internal jugular venous sampling. Norepinephrine was released into the cerebrovascular circulation in both hypertensive patients and healthy volunteers and was present after administration of the ganglion blocker trimethaphan and in patients with sympathetic nervous failure, indicating that brain neurons and not cerebrovascular sympathetic nerves were the probable source. Although differing among hypertensive patients, norepinephrine spillover on average was higher in the hypertensive patients (153 +/- 41 pmol/min) than in healthy subjects (59 +/- 12 pmol/min; p less than 0.05), and was elevated in six of 17 patients, in whom the accompanying whole body norepinephrine spillover rate was higher than in the remaining 11 patients (p less than 0.01). To test for a possible link between brain norepinephrine release and human sympathetic nervous function, the effect of the tricyclic antidepressant desipramine (0.3 mg/kg i.v.) on both brain and whole body norepinephrine spillover was measured in healthy volunteers. Desipramine lowered the cerebrovascular spillover of norepinephrine, its precursor dihydroxyphenylalanine, and its metabolite dihydroxyphenylglycol by 50-80% and produced a mean fall of 35% in whole body norepinephrine spillover. One interpretation of these results is that human sympathetic nerve firing is dependent on norepinephrine release within the brain and that increased cerebral norepinephrine release may possibly be present in some patients with essential hypertension, underlying their higher sympathetic nerve firing rates.
Ferrier
C
C
Alfred and Baker Medical Unit, Alfred Hospital, Melbourne, Australia.
Esler
M D
MD
Eisenhofer
G
G
Wallin
B G
BG
Horne
M
M
Cox
H S
HS
Lambert
G
G
Jennings
G L
GL
D002560:Cerebrovascular Circulation; D004295:Dihydroxyphenylalanine / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007601:Jugular Veins; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D012016:Reference Values; D014294:Trimethaphan / Q000494:pharmacology
D008734:Methoxyhydroxyphenylglycol; D004295:Dihydroxyphenylalanine; D014294:Trimethaphan; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine