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.