Inhibition of glucagon improves splanchnic hyporesponse to terlipressin in cirrhotic rats with blood retention in the gastric lumen.
OBJECTIVE
Portal hypotensive effect of terlipressin is less effective when given during hemorrhage than in stable state. Blood retention in the stomach can induce splanchnic hyperemia which is mainly a consequence of an increased glucagon release. This study was undertaken to evaluate whether gastric blood retention contributes to the splanchnic hyporesponse to terlipressin.


METHODS
Plasma glucagon determination was performed under basal conditions and after intragastric blood gavage in sham-operated and cirrhotic rats. Additionally, splanchnic hemodynamic effects to terlipressin were measured in blood-gavaged cirrhotic rats with or without glucagon antiserum or octreotide infusion. Another set of air-gavaged cirrhotic rats was included for comparison.


RESULTS
Plasma glucagon level increased in both sham-operated and cirrhotic rats following blood gavage. Compared to air-gavaged cirrhotic rats, splanchnic hyporesponse to terlipressin was observed in cirrhotic rats receiving intragastric blood gavage. However, this splanchnic hyporesponse to terlipressin in blood-gavaged cirrhotic rats was overcome by glucagon antiserum or octreotide infusion.


CONCLUSIONS
Intragastric blood gavage induced an elevation of plasma glucagon level and led to a splanchnic hyporesponse to terlipressin. Glucagon antiserum or octreotide administration overcame this hyporesponse. Excessive release of circulating glucagon may be an important factor for splanchnic hyporesponse to terlipressin in cirrhotic portal hypertension during hemorrhage.
Yang
Ying-Ying
YY
Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
Lin
Han-Chieh
HC
Huang
Yi-Tsau
YT
Hou
Ming-Chih
MC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lee
Shou-Dong
SD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001769:Blood; D004357:Drug Synergism; D005751:Gastric Lavage; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D013270:Stomach / Q000098:blood supply*; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000906:Antibodies; D005765:Gastrointestinal Agents; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin; D005934:Glucagon; D015282:Octreotide