Surgical and pharmacological dissociation of cardiovascular and emetic responses to intragastric CuSO4.
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.
Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145.
M T
MT
Makale
G L
GL
King
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003300:Copper / Q000008:administration & dosage* / Q000494:pharmacology; D019327:Copper Sulfate; D003714:Denervation; D004386:Duodenum; D004639:Emetics / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007441:Intubation, Gastrointestinal; D007813:Laparotomy; D008297:Male; D011184:Postoperative Period; D013153:Splanchnic Nerves; D013270:Stomach; D014628:Vagotomy
D000959:Antihypertensive Agents; D001286:Atropine Derivatives; D004639:Emetics; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D003300:Copper; C006649:methylatropine; D019327:Copper Sulfate