Preventive effect of atropine on indomethacin-induced gastrointestinal mucosal and vascular damage in rats.
The protective effect of 'chemical vagotomy' (atropine given in three doses: 0.1, 0.5 and 1.0 mg/kg i.p.) was examined on indomethacin (IND, 20 mg/kg s.c.)-induced macroscopic gastrointestinal (GI) mucosal erosions and changes of vascular permeability in the stomach and three equal parts of small intestine and colon in rats. The different doses of atropine were administered at 0, 5, 10, 15 and 20 h after IND administration, then the number and severity of lesions were noted and the vascular damage was measured by Evans blue extravasation into the mucosa and intraluminal juice at 24 h after the IND treatment. Our results indicate that atropine ('chemical vagotomy') dose-dependently and significantly decreases the IND-induced mucosal erosions and vascular permeability in the vagal nerve-innervated parts of GI tract (i.e. the stomach, small intestine and proximal colon). Atropine in 0.5 and 1.0 mg/kg doses has a significantly higher protective effect on the vascular damage than on the macroscopic mucosal lesions in the stomach, small intestine and proximal colon. The vascular permeability is only one of those factors which have a role in the appearance of the GI mucosal erosions after IND treatment. These results suggest that the decrease of vascular permeability is involved in the protective effect of atropine against IND-induced GI mucosal damage.
Karádi
O
O
First Department of Medicine, Medical University of Pécs, Hungary.
Abdel-Salam
O M
OM
Bódis
B
B
Mózsik
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000293:injuries; D004305:Dose-Response Relationship, Drug; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries*; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries*; D007421:Intestine, Small / Q000187:drug effects / Q000293:injuries; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018727:Muscarinic Antagonists; D012709:Serum Albumin; D001285:Atropine; D007213:Indomethacin