Chronic indomethacin treatment enhances the portal-systemic collateral vascular response to vasopressin in bile-duct ligated rats.
BACKGROUND
Liver cirrhosis is often accompanied by portal-systemic collateral formation with hemorrhage and encephalopathy. Prostacyclin participates in hyperdynamic circulation and vascular hyporeactiveness to vasoconstrictors in cirrhosis. It has been shown that arginine vasopressin (AVP) induces direct collateral vasoconstriction in portal hypertensive rats, which is potentiated by indomethacin preincubation. However, the influence of chronic indomethacin administration in cirrhosis remains unexplored.


METHODS
This study was performed on male Sprague-Dawley rats with liver cirrhosis induced by common bile duct ligation. They received subcutaneous indomethacin (5 mg/kg/day) or distilled water (control) injection from the 36th to 42nd day after operation. On the 43rd day, systemic and portal hemodynamics were evaluated and the following experiments were performed with an in situ collateral perfusion model: in the first series, concentration-response curves to AVP (10(-10) to 10(-7) M) were obtained; in the second series, flow-pressure curves were plotted (Krebs solution, 6-18 mL/min), where the slope represents an index of collateral vascular resistance (the higher the resistance, the smaller the amount of shunting vessels, that is, the lower the degree of shunting).


RESULTS
The mean arterial pressure and portal pressure were similar between indomethacin and control groups (p > 0.05). Indomethacin elevated the collateral perfusion pressure to AVP (3 x 10(-9), 10(-8) M, p < 0.05) but did not influence the slope of the flow-pressure curve (p > 0.05).


CONCLUSIONS
In bile duct-ligated cirrhotic rats, indomethacin improves the portal-systemic collateral vascular responsiveness to AVP without alleviating the severity of shunting.
Huang
Hui-Chun
HC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R O C.
Wang
Sun-Sang
SS
Chang
Ching-Chih
CC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chih
MC
Lu
Rei-Hwa
RH
Lee
Shou-Dong
SD
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001652:Bile Ducts; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000627:therapeutic use*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects*
D001127:Arginine Vasopressin; D007213:Indomethacin