Chronic cyclooxygenase blockade enhances the vasopressin responsiveness in collaterals of portal hypertensive rats.
OBJECTIVE
Collateral vascular responsiveness to vasoconstrictors may be crucial in the management of acute variceal bleeding. In an in situ perfusion model, arginine vasopressin (AVP) has been shown to cause a direct vasoconstrictive effect on portal-systemic collaterals and this effect is enhanced by preincubation of indomethacin (INDO). The purpose of this study was to investigate the effects of chronic INDO administration on the portal-systemic collateral responsiveness to AVP and the degree of portal-systemic shunting in portal hypertensive rats.


METHODS
Rats with partial portal vein ligation randomly received daily subcutaneous injections with INDO (5 mg/kg) or distilled water (control group) 2 days prior to until 7 days after ligation. Systemic and portal hemodynamics was evaluated on the 8th day. Using an in situ collateral perfusion model, AVP (10(-10)-10(-7) M) at a constant flow rate (20 ml/min) was applied. In another series, Krebs solution with different flow rates (5-30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances--the higher resistances indicate fewer collaterals.


RESULTS
Mean arterial pressure and portal pressure were not significantly different between the INDO-treated group and the control group (p>0.05). In the first series of experiments, INDO treatment increased the collateral perfusion pressure to AVP at 10(-8) M, 3x10(-8) M, and 10(-7) M (p<0.05). In the second series, INDO did not change collateral vascular resistance, which suggests that the degree of shunting was not altered.


CONCLUSIONS
Chronic INDO treatment improves the collateral vascular responsiveness to AVP without ameliorating portal-systemic shunting in portal hypertensive rats.
Huang
Hui-Chun
HC
Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Wang
Sun-Sang
SS
Chen
Yi-Chou
YC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chih
MC
Chang
Ching-Chih
CC
Lee
Shou-Dong
SD
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D006975:Hypertension, Portal / Q000503:physiopathology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D011168:Portal System / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D001127:Arginine Vasopressin; D007213:Indomethacin