Role of acute elevation of portal venous pressure by exogenous glucagon on gastric mucosal injury in rats with portal hypertension.
Time-course studies revealed the increased susceptibility of the gastric mucosa to noxious injury in portal hypertension correlates with the level of elevated portal venous pressure and hyperglucagonemia. Whether acute elevation of portal venous pressure by exogenous glucagon aggravates such injury is not known. We tested the hypothesis that glucagon in a dose sufficient to acutely elevate portal venous pressure aggravates noxious injury of the gastric mucosa in rats with portal hypertension. Infusion of a portal hypotensive dose of somatostatin should reverse these changes. In anesthetized rats with portal vein ligation, glucagon, somatostatin or the combination was administered intravenously in a randomized, coded fashion. Acidified ethanol-induced gastric mucosal injury was determined. Portal venous pressure and gastric mucosal perfusion and oxygenation (reflectance spectrophotometry) were monitored to confirm the effects of the respective intravenous treatments. Exogenous glucagon exacerbated acidified ethanol-induced gastric mucosal injury. The exacerbation was attenuated by somatostatin. These changes paralleled the portal hypertensive and hypotensive effects of glucagon and somatostatin, respectively. Our data suggest that a unique mechanism is triggered with the onset of portal hypertension. In an antagonistic manner, glucagon and somatostatin modulate this novel mechanism that controls portal venous pressure and susceptibility of the gastric mucosa to noxious injury.
Tsui
C P
CP
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
Sung
Joseph J Y
JJ
Leung
Felix W
FW
D000818:Animals; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000633:toxicity; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000032:analysis; D011169:Portal Vein / Q000503:physiopathology* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013004:Somatostatin / Q000627:therapeutic use; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D014690:Venous Pressure
D010108:Oxyhemoglobins; D000431:Ethanol; D013004:Somatostatin; D005934:Glucagon; D006851:Hydrochloric Acid