title: The roles of angiotensin II receptors in the portosystemic collaterals of portal hypertensive and cirrhotic rats.
abstract: OBJECTIVE
  In liver cirrhosis/portal hypertension, collaterals as varices may bleed and are influenced by vasoresponsiveness. An angiotensin blockade ameliorates portal hypertension but the influence on collaterals is unknown.
  
  
  METHODS
  Portal hypertension and cirrhosis were induced by portal vein (PVL) and common bile duct ligation (BDL). Hemodynamics, real-time PCR of angiotensin II receptors (AT(1)R, AT(2)R) in the left adrenal vein (LAV, sham) and splenorenal shunt derived from LAV (PVL, BDL) were performed. With an in situcollateral perfusion model, angiotensin II vasoresponsiveness with different preincubations was evaluated: (1) vehicle; (2) AT(1)R blocker losartan; (3) losartan plus nonselective nitric oxide synthase (NOS) inhibitor (N(ω)-nitro-L-arginine); (4) AT(2)R blocker PD123319; (5) PD123319 plus N(ω)-nitro-L-arginine; (6) N(ω)-nitro-L-arginine, and (7) losartan plus inducible NOS inhibitor aminoguanidine.
  
  
  RESULTS
  LAV AT(1)R and AT(2)R expression decreased in PVL and BDL rats. Losartan attenuated angiotensin II-elicited vasoconstriction but PD123319 had no effect. N(ω)-nitro-L-arginine but not aminoguanidine reversed the losartan effect.
  
  
  CONCLUSIONS
  Angiotensin receptors are downregulated in the collateral vessel of portal hypertensive and cirrhotic rats. The AT(1)R blockade attenuates the angiotensin II vasoconstrictive effect, suggesting AT(1)R mediates collateral vasoconstriction and the influence of AT(2)R is negligible. The lack of aminoguanidine influence indicates that endothelial NOS participates in the losartan effect.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Teng
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Lee
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Chiao-Lin
authors.initials: CL
authors.lastname: Chuang
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D015536:Down-Regulation; D006146:Guanidines / Q000494:pharmacology; D006975:Hypertension, Portal / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008026:Ligation; D008103:Liver Cirrhosis / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011169:Portal Vein / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D006146:Guanidines; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D019808:Losartan; C004479:pimagedine