Effect of Ganglion Blockade on Cerebrospinal Fluid Norepinephrine

Abstract

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.

Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone

“…Third, NE inhibits the medial prefrontal cortex, which normally restrains the HPA axis (8). Fourth, it now clearly is established that the sympathetic nervous system exerts extrapituitary modulation of adrenocortical corticosteroid secretion, especially during chronic stress (8,(35)(36)(37)(38)(39).…”

Increased norepinephrine spillover into the jugular veins in essential hypertension.

“…That some norepinephrine may have originated from cerebrovascular nerves cannot be excluded with certainty. In dogs, ganglionic blockade with trimethaphan has been reported to decrease the concentration of norepinephrine in cerebrospinal fluid, 31 a finding taken to indicate that it is postganglionic sympathetic nerve endings that are the major source of norepinephrine in cerebrospinal fluid. Supporting our concept of a predominantly neuronal origin of the norepinephrine released into the cerebral circulation is the fact that in our patients with idiopathic peripheral autonomic insufficiency who had sympathetic nerves damaged by disease, cerebrovascular norepinephrine spillover was undiminished even though, as expected, total body norepinephrine spillover was markedly reduced.…”

Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder

“…For example, norepinephrine in plasma and in cerebrospinal fluid (CSF) are derived from largely, but not completely [Goldstein et al, 1987] disparate sources; therefore, dissociation between peripheral and CNS norepinephrine concentrations can take place. Results of serial CSF and plasma sampling studies in humans indicate that plasma concentrations of norepinephrine predict only about 20% of the cerebrospinal fluid (i.e.…”