The source of
norepinephrine (NE) in CSF has been unclear. It has been suggested that CSF NE indicates central neural noradrenergic tone and is determined differently from plasma NE. If CSF NE depended specifically on NE release in the CNS, then interference with ganglionic neurotransmission would be expected to decrease plasma NE but not CSF NE.
Hypotension caused by ganglionic blockade might be expected to increase CSF NE reflexively. We infused the
ganglion blocker,
trimethaphan, intravenously into anesthetized dogs and measured the effects on mean arterial blood pressure (MAP) and on cisterna magna CSF levels of NE. The results were compared with those obtained on administration of saline,
clonidine (2 micrograms/kg),
yohimbine (0.25 mg/kg), or
nitroprusside and with those obtained when
hypotension during
ganglion blockade was prevented by concurrent treatment with
phenylephrine.
Trimethaphan decreased MAP by 40%, arterial NE by 64%, and CSF NE by 61%.
Nitroprusside administered intravenously to produce the same 40% depressor response increased arterial NE by 612% and CSF NE by 155%. Prevention of
ganglion blockade-
induced hypotension using
phenylephrine did not prevent the decrease in CSF NE caused by
trimethaphan, and when
phenylephrine was discontinued, the resulting
hypotension was not associated with increases in CSF NE. The similar decreases in plasma NE and CSF NE during ganglionic blockade, and the abolition of reflexive increases in CSF NE during
hypotension in
ganglion-blocked subjects, cast doubt on the hypothesis that CSF NE indicates central noradrenergic tone and are consistent instead with at least partial derivation of CSF NE from postganglionic sympathetic nerve endings.