Intragastric nicotine protection against 40% ethanol injury in rat stomach. Role of ganglionic stimulation or blockade.
Intragastric nicotine (4 mg/kg) protects against 40% ethanol-induced gastric mucosal injury and raises mean blood pressure. We postulated that this protective effect was mediated by the ganglionic stimulatory property of nicotine and therefore could be abolished by ganglionic blockers. Rats were pretreated with intraperitoneal hexamethonium (10 mg/kg) or mecamylamine (2 mg/kg) to block peripheral or central autonomic ganglia, respectively. Intragastric vehicle or nicotine (4 mg/kg) was then administered. The total lengths of the linear gastric corpus mucosal lesions induced by intragastric 40% ethanol were measured by an unbiased observer using a caliper. The results showed that both intraperitoneal hexamethonium and mecamylamine pretreatments protected against 40% ethanol-induced gastric mucosal injury. Neither modified the protective effect of intragastric nicotine. The protective effect of hexamethonium and mecamylamine was associated with a significant increase in the volume of gastric mucus and gastric juice. The increase in the volume of gastric content (mucus and juice) was partially responsible for the protective effect of these ganglionic blockers. In a separate experiment, intraperitoneal nicotine (4 mg/kg) also protected against 40% ethanol-induced gastric mucosal injury and raised mean blood pressure. These data indicate that the protection against 40% ethanol-induced gastric mucosal injury is not unique to intragastric nicotine. Such protection can be induced by ganglionic blocking doses of hexamethonium and mecamylamine, or a ganglionic stimulatory dose of intraperitoneally administered nicotine. Whether ganglionic stimulation or blockade plays a role in the mechanism of intragastric nicotine protection, however, remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Service, Sepulveda Veterans Administration Medical Center 91343.
K
K
Endoh
J
J
Kao
M
M
Baker
F W
FW
Leung
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005728:Ganglia, Sympathetic / Q000502:physiology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005730:Ganglionic Blockers; D005731:Ganglionic Stimulants; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D000431:Ethanol; D008464:Mecamylamine; D009538:Nicotine