title: Effect of 1-week losartan administration on bile duct-ligated cirrhotic rats with portal hypertension.
abstract: OBJECTIVE
  Nitric oxide and angiotensin play important roles in the pathogenesis of the hemodynamic derangement in cirrhosis and portal hypertension. The hemodynamic effects of losartan, an angiotensin II type 1 receptor antagonist, in cirrhotic patients with portal hypertension are conflicting. This study was undertaken to explore the possible mechanism of action of losartan on portal hypertension in cirrhotic rats produced by bile duct ligation (CBL).
  
  
  METHODS
  Three weeks after surgery, CBL and sham-operated rats randomly received vehicle or losartan (3 mg/kg per 12 h by gavage) for 1 week. Hemodynamic values, hormone levels, and aortic eNOS protein expression were measured after drug administration.
  
  
  RESULTS
  In CBL rats, 1-week losartan treatment decreased portal pressure and ameliorated hyperdynamic circulation associated with a blunted vascular response to N(omega)-nitro-L-arginine methyl ester infusion. The hematocrit increased and the plasma volume, aldosterone, plasma renin activity, norepinephrine, and nitrate and nitrite levels decreased. The eNOS protein expression was reduced in CBL rats receiving losartan compared with those receiving vehicle.
  
  
  CONCLUSIONS
  One-week losartan treatment in CBL rats decreased portal pressure and ameliorated hyperdynamic circulation. In addition to the suppression of renin-angiotensin axis, the reduced aortic eNOS protein expression may play a partial role for the mechanism of action of losartan in CBL rats.
authors: Division of Gastroenterology, Department of Medicine, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan.
authors: Ying-Ying
authors: YY
authors: Yang
authors: Han-Chieh
authors: HC
authors: Lin
authors: Yi-Tsau
authors: YT
authors: Huang
authors: Tzung-Yen
authors: TY
authors: Lee
authors: Ming-Chih
authors: MC
authors: Hou
authors: Fa-Yauh
authors: FY
authors: Lee
authors: Ren-Shyan
authors: RS
authors: Liu
authors: Full-Young
authors: FY
authors: Chang
authors: Shou-Dong
authors: SD
authors: Lee
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003135:Common Bile Duct; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006400:Hematocrit; D006975:Hypertension, Portal / Q000097:blood / Q000188:drug therapy*; D008026:Ligation; D008102:Liver Circulation / Q000502:physiology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000097:blood; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D009566:Nitrates; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D012083:Renin; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine