AJP - Regulatory, Integrative and Comparative Physiology, Vol 263, Issue 2 284-R291, Copyright © 1992 by American Physiological Society
Surgical and pharmacological dissociation of cardiovascular and emetic responses to intragastric CuSO4
M. T. Makale and G. L. King
Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145.
Under control (intact and laparotomized) conditions, arterial pressure of
urethan-anesthetized ferrets rose significantly in response to intragastric
copper sulfate (CuSO4; 10 ml of 5 mg/ml). CuSO4 was emetic 75-90% of the
time, and a cardiovascular response always immediately preceded and
accompanied emetic responses. The cardiovascular response was significantly
reduced or abolished by hexamethonium (0.35 mg/kg) pretreatment combined
with atropine methyl bromide (1 mg/kg). Addition of the alpha 2-receptor
antagonist 2,3-dichloro-alpha-methylbenzylamine HCl (DCMB, 10 mg/kg) and
the beta-receptor antagonist propranolol (3 mg/kg) to the hexamethonium and
atropine combination prevented its reduction of the cardiovascular
response. Given individually, these agents did not alter cardiovascular
response, nor did yohimbine (0.30 mg/kg), RS(+/-)-zacopride (0.30 mg/kg),
or granisetron (0.50 mg/kg). Only RS(+/-)-zacopride significantly reduced
incidence of emesis. Atropine methyl bromide alone, with hexamethonium, or
with hexamethonium, propranolol, and DCMB significantly delayed the first
emetic episode. Conversely, bilateral abdominal vagotomy significantly
reduced the number of vomiting animals without affecting cardiovascular
response. These results suggest that the neural pathways mediating the two
events are not identical. In another series of experiments, a significantly
greater proportion of animals vomited in response to intragastric CuSO4
than to intraduodenal CuSO4, suggesting that the primary site of CuSO4
action in the ferret is the stomach.
