title: Chronic cyclooxygenase blockade enhances the vasopressin responsiveness in collaterals of portal hypertensive rats.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Yi-Chou
authors.initials: YC
authors.lastname: Chen
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Full-Young
authors.initials: FY
authors.lastname: Chang
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Hou
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: 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
chemical_list: D016861:Cyclooxygenase Inhibitors; D001127:Arginine Vasopressin; D007213:Indomethacin