Effects of intracerebroventricular injection of indomethacin on adaptive gastric cytoprotection in the conscious rat.
We investigated the role of prostaglandins in the central nervous system for the adaptive gastric cytoprotection in male Wistar rats with chronic intracerebroventricular cannulas. Three, 50, 200, or 500 micrograms of indomethacin or vehicle alone was injected via the intracerebroventricular (central) or intraperitoneal route 1 h before oral administration of 20% ethanol. The animals were then given 1 ml of absolute ethanol 15 min later. One hour later, gastric mucosal damage and plasma indomethacin concentrations were measured. Pretreatment with 50-500 micrograms of indomethacin abolished adaptive gastric cytoprotection induced by 20% ethanol in a dose-dependent fashion, regardless of the route of administration. Central administration of 3 micrograms indomethacin resulted in a more than twofold increase in mucosal damage compared with intraperitoneal administration. Plasma indomethacin concentrations were increased dose-dependently. However, plasma levels were lower in rats administered centrally than those peripherally at a dose of 50 micrograms indomethacin or more. On the other hand, plasma indomethacin concentrations did not differ between central and intraperitoneal administration of 3 micrograms indomethacin. Measurement of gastric mucosal blood flow revealed that central administration of 3 micrograms indomethacin reduced gastric mucosal blood flow, whereas intraperitoneal administration of an identical dose had no effect. These results suggest that central prostaglandins may contribute to adaptive gastric cytoprotection, possibly by altered gastric mucosal blood flow.
Kato
K
K
Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Kuwayama
H
H
Matsuo
Y
Y
Murai
I
I
Nakagawa
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply* / Q000294:innervation; D007213:Indomethacin / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects
D000431:Ethanol; D007213:Indomethacin