The antilesion actions of anticholinergic agents on ethanol-induced injury in rat stomachs: the importance of gastric vascular integrity and tonicity.
1. The antilesion actions of two antimuscarinic drugs on ethanol-induced gastric injury and mucosal integrity were examined in male rats. Histological examinations were made and gastric emptying rates determined after in vivo administration of the drugs to conscious rats. In anaesthetized rats, with an ex vivo gastric chamber, effects on gastric transmucosal potential difference, Evan's blue leakage and Na+ output were examined. 2. In conscious animals, atropine (1 mgkg-1, i.p.) and pirenzepine (1 mgkg-1, i.p.) both significantly reduced macroscopic lesion formation, but not microscopic damage and functional alterations, caused by orally administered absolute ethanol. Moreover, these drugs did not show any effect on the basal gastric adherent mucus level, nor the depleting action of ethanol on both adherent mucus and the mucosal mucus layer. Nevertheless, both atropine and pirenzepine significantly reduced gastric emptying rate. 3. In anaesthetized animals, pirenzepine but not atropine increased the basal transmucosal potential difference (PD); however, it could not prevent the ethanol-induced drop in PD. Furthermore, the inhibitory action of ethanol on sodium ion output from the gastric mucosa was not attenuated by these drugs. Pirenzepine, however, significantly lessened the increase in vascular permeability caused by 100% ethanol. This action was not shared by atropine. 4. These findings indicate that both atropine and pirenzepine exert their antilesion actions through the relaxation of the stomach. Pirenzepine also preserves the integrity of the gastric mucosal vasculature, which is distinct from the action of atropine. The protective action of these drugs occurs only at the macroscopic level.
Ko
J K
JK
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Cho
C H
CH
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000009:adverse effects*; D001285:Atropine / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects*; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000473:pathology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000891:Anti-Infective Agents, Local; D018727:Muscarinic Antagonists; D010890:Pirenzepine; D000431:Ethanol; D001285:Atropine