Excitotoxin-induced degeneration of rat vagal afferent neurons.
The inferior vagal or nodose ganglion contains the perikarya of vagal afferent neurons that function as cardiopulmonary and abdominal visceral receptors as well as aortic arch baroreceptors. In this study we have sought to utilize the axon-sparing properties of the excitotoxins kainic acid, N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-4-isoxazolepropionic acid to destroy the perikarya of these sensory neurons and thus selectively de-afferent the vagus in the rat. Kainic acid (0.5 nmol/microliters, 2 X 2 microliters) was applied topically to both nodose ganglia and the rats were allowed to recover for 7-8 days. Baroreceptor heart rate reflex activity was assessed in these conscious rats. Baroreceptor heart rate reflex gain was reduced (-51%) in kainic acid-treated rats, as was the maximal reflex bradycardia induced by the pressor agent, phenylephrine. Kainic acid treatment did not alter resting mean arterial pressure or heart rate. Vagal efferent neurons were spared by kainic acid treatment since bradycardic responses to electrical stimulation of the peripheral end of a cut vagus were not impaired. Histological studies showed marked destruction of perikarya within the nodose ganglia of kainic acid-treated rats: inflammatory and degenerative changes were evident at 2 days, and at 10 days there was considerable loss of neuronal cell bodies, but sparing of axons. Topical application to the nodose ganglion of alpha-methyl-DL-aspartic acid (6.8 nmol/microliters, 2 X 2 microliters), a non-excitotoxic dicarboxylic acid, failed to alter baroreflex sensitivity or produce perikaryal degeneration in nodose ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)
Lewis
S J
SJ
University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Victoria, Australia.
Verberne
A J
AJ
Louis
C J
CJ
Jarrott
B
B
Beart
P M
PM
Louis
W J
WJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D009410:Nerve Degeneration; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid