The mucoid cap over superficial gastric damage in the rat. A high-pH microenvironment dissipated by nonsteroidal antiinflammatory drugs and endothelin.
The ability of the "mucoid cap" of mucus, fibrin, and cellular debris that forms over sites of superficial gastric damage to provide a relatively high-pH microenvironment was investigated in the rat. Furthermore, the effects of administration of nonsteroidal antiinflammatory drugs or reduction of mucosal blood flow on this microenvironment were investigated. Superficial mucosal damage induced by a 2-minute exposure to hypertonic saline produces a mucoid cap that has a pH of 4-6 despite the presence in the lumen of a solution of acid with a pH of less than 1. This relatively high-pH microenvironment remained even when the exposure to 0.15-mol/L HCl was continued for as long as 1 hour. Intraperitoneal administration of indomethacin (5 mg/kg) or naproxen (10 mg/kg) resulted, within 10-25 minutes, in complete dissipation of this high-pH microenvironment, with the subsequent development of hemorrhagic erosions. These effects of indomethacin and naproxen occurred subsequent to significant inhibition of gastric prostaglandin synthesis by these agents. Rapid dissipation of the pH gradient could also be produced by brief (30-second) clamping of the arterial blood supply to the chambered mucosa or by systemic administration of a vasoconstrictor (endothelin-1), in both cases resulting in the development of hemorrhagic erosions. These results show that the mucoid cap over sites of superficial damage provides a relatively high-pH microenvironment and that dissipation of this microenvironment by inhibitors of prostaglandin synthesis or by reduction of mucosal blood flow can convert sites of superficial mucosal injury to hemorrhagic erosions. Such inhibitory effects might contribute to the ulcerogenic actions of nonsteroidal antiinflammatory drugs.
Gastrointestinal Research Group, University of Calgary, Alberta, Canada.
J L
JL
Wallace
G W
GW
McKnight
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D005337:Fibrin / Q000502:physiology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009093:Mucus / Q000502:physiology; D009288:Naproxen / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016232:Endothelins; D010455:Peptides; D009288:Naproxen; D005337:Fibrin; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin