Guanethidine adrenergic neuropathy: an animal model of selective autonomic neuropathy.
Chronic administration of guanethidine to adult rats induces a selective autoimmune adrenergic neuropathy. Physiological and biochemical features of this disorder in the peripheral nervous system were explored in young adult Sprague-Dawley rats given daily intraperitoneal guanethidine monosulfate for 5 weeks. Control rats received daily saline injections. The guanethidine-treated animals gained less weight, had ptosis, and had a lower mean arterial blood pressure in the supine and upright tilted positions. Norepinephrine was depleted in the peroneal, sural, tibial, and vagal nerves, the nutrient artery to the tibial nerve and in the superior cervical sympathetic ganglion of the drug-treated animals. On light microscopy, there was an inflammatory cell infiltrate and neuron loss in the superior cervical ganglion. Caudal and sciatic-tibial nerve conduction values were well preserved in the guanethidine-treated animals as was the 'C' potential derived from unmyelinated vagal fibers recorded in an in vitro chamber. The 'C' potential recorded from the cervical sympathetic trunk, however, was reduced in amplitude correlating with the loss of norepinephrine content in the harvested contralateral superior cervical sympathetic ganglion. The findings further support the view that guanethidine produces a selective adrenergic neuropathy in the rat--providing a useful standard with which to gauge autonomic involvement in other models of neuropathy. In addition, loss of the cervical sympathetic 'C' potential suggests that this presumed preganglionic structure also contains postganglionic adrenergic fibers.
Zochodne
D W
DW
Department of Neurology, Mayo Foundation, Rochester, MN 55905.
Ward
K K
KK
Low
P A
PA
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction; D009498:Neurotoxins; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000503:physiopathology*; D013979:Tibial Nerve / Q000503:physiopathology*
D009498:Neurotoxins; D006145:Guanethidine