Effects of prostacyclin inhibition on splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension.
BACKGROUND
Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis and hemorrhage. Similar findings exist with infusion of glypressin (a long-acting vasopressin analogue), and this phenomenon could be ameliorated by inhibition of nitric oxide (NO) synthase. Besides NO, excessive formation of prostacyclin (PGI2) has been shown to play an important role in the development of hyperdynamic circulation and the mediation of hyporeactivity to vasoconstrictors in portal-hypertensive states. This study was designed to investigate whether the blockade of PGI2 activity by indomethacin infusion could enhance the portal-hypotensive effect of glypressin in portal-hypertensive rats with bleeding.


METHODS
Portal hypertension was induced by partial portal vein ligation (PVL). Fourteen days after operation systemic and portal hemodynamics were measured in stable or bleeding PVL rats receiving intravenous glypressin (0.07 mg/kg) or indomethacin (5 mg/kg) followed by glypressin infusion. In rats with a hypotensive hemorrhage 4.5 ml of blood was withdrawn, and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin.


RESULTS
Splanchnic hyposensitivity to glypressin was shown in hemorrhage-transfused PVL rats. Indomethacin infusion did not cause significant systemic and portal-hemodynamic changes in bleeding PVL rats (P > 0.05). The addition of indomethacin significantly enhanced the portal-hypotensive effects of glypressin and potentiated the increases in mean arterial pressure induced by glypressin infusion in bleeding PVL rats.


CONCLUSIONS
The improvement of splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension by the administration of indomethacin suggests that PGI2 has in the development of this hyposensitivity.
Wang
S S
SS
Dept. of Medicine, Taipei Veterans General Hospital, Taiwan.
Chu
C J
CJ
Lee
F Y
FY
Wu
S L
SL
Lin
H C
HC
Chan
C C
CC
Chang
F Y
FY
Lee
S D
SD
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001803:Blood Transfusion; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006471:Gastrointestinal Hemorrhage; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D000077585:Terlipressin
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D008236:Lypressin; D000077585:Terlipressin; D007213:Indomethacin