Prostaglandin modulation of the gastric vasculature and mucosal integrity in cirrhotic rats.
Gastric bleeding is a frequent occurrence in cirrhotic patients and may be related to altered microcirculatory responses to luminal irritants and/or vasoactive mediators. Because gastric prostaglandin synthesis has been reported to be altered in cirrhosis, we have examined the role of prostaglandins in modulating gastric perfusion velocity and mucosal integrity in cirrhotic rats. Cirrhosis was induced by bile duct ligation. Gastric perfusion velocity was measured in an ex vivo gastric chamber preparation by laser-Doppler flowmetry. The responsiveness of the mucosa to topical application of 20% ethanol was assessed. Effects of pretreatment with indomethacin or misoprostol were also determined. Gastric and hepatic prostaglandin E2 syntheses were significantly depressed (by approximately 60%) in cirrhotic vs. normal rats. Administration of indomethacin (7.5 mg/kg) to normal rats did not significantly affect gastric perfusion velocity, but in cirrhotic rats it caused a 45% reduction (P < 0.05). Topically applied misoprostol produced significantly greater (2- to 5-fold) increases in gastric perfusion velocity in cirrhotics than in controls. Cirrhotic rats were significantly more susceptible to gastric injury induced by topically applied 20% ethanol than were controls. These results suggest that gastric perfusion velocity in cirrhotic rats is modulated by endogenous prostaglandins to a much greater degree than in controls. Gastric vascular hyperresponsiveness to misoprostol may be attributable to an adaptive response to depressed endogenous prostaglandin synthesis in the cirrhotic animals.
Beck
P L
PL
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
McKnight
W
W
Lee
S S
SS
Wallace
J L
JL
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001808:Blood Vessels / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000098:blood supply*
D011453:Prostaglandins; D016595:Misoprostol; D000431:Ethanol; D015232:Dinoprostone; D007213:Indomethacin