Inhibition of prostacyclin by indomethacin ameliorates the splanchnic hyposensitivity to glypressin in haemorrhage-transfused common bile duct-ligated rats.
Prostacyclin (PGI2) is an important contributor to the mediation of hyporeactivity to vasoconstrictors and the development of hyperdynamic circulation in portal hypertensive states. Inhibition of PGI2 synthesis in haemorrhage-transfused partially portal vein-ligated rats could ameliorate the splanchnic hyposensitivity to glypressin, a long-acting vasopressin analogue. This study investigated whether the hyposensitivity to glypressin also exists in rats with common bile duct ligation (BDL) and whether the inhibition of PGI2 synthesis by indomethacin could potentiate the portal-hypotensive effect of glypressin in bleeding BDL rats. Two series of BDL rats were used. Series 1 investigated the haemodynamic effects of low dose glypressin (0.07 mg kg-1) in BDL rats with or without bleeding by catheterization. In series 2, haemodynamic parameters were measured in stable or bleeding BDL rats that were receiving intravenously high dose glypressin (0.2 mg kg-1) or indomethacin (5 mg kg-1) followed by high dose glypressin. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin. Splanchnic hyposensitivity to glypressin was demonstrated in haemorrhage-transfused BDL rats receiving high, but not low, doses of glypressin. Indomethacin infusion did not cause significant systemic and portal haemodynamic changes in bleeding BDL rats (P > 0.05). The addition of indomethacin significantly enhanced the portal-hypotensive effects of glypressin (P < 0.05) and potentiated the increases in mean arterial pressure induced by glypressin infusion (P < 0.001) in bleeding BDL rats. Splanchnic hyposensitivity to glypressin observed in haemorrhage-transfused BDL rats could be ameliorated by the addition of indomethacin, suggesting a role of endogenous PGI2 in its pathophysiology.
Lee
F Y
FY
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No.201, Sec. 2, Shih-Pai Road, Taipei, Taiwan 11217, Republic of China. fylee@vghtpe.gov.tw
Chu
C J
CJ
Wang
S S
SS
Chang
F Y
FY
Lin
H C
HC
Hou
M C
MC
Chan
C C
CC
Wu
S L
SL
Chen
C T
CT
Huang
H C
HC
Lee
S D
SD
D000818:Animals; D001803:Blood Transfusion; D003135:Common Bile Duct / Q000601:surgery; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D006470:Hemorrhage / Q000628:therapy; D006975:Hypertension, Portal / Q000209:etiology; D007213:Indomethacin / Q000494:pharmacology*; D008026:Ligation; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects*; D000077585:Terlipressin; D014661:Vasoconstriction / Q000187:drug effects*
D008236:Lypressin; D000077585:Terlipressin; D011464:Epoprostenol; D007213:Indomethacin