Effect of 1-week losartan administration on bile duct-ligated cirrhotic rats with portal hypertension.
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.
Yang
Ying-Ying
YY
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.
Lin
Han-Chieh
HC
Huang
Yi-Tsau
YT
Lee
Tzung-Yen
TY
Hou
Ming-Chih
MC
Lee
Fa-Yauh
FY
Liu
Ren-Shyan
RS
Chang
Full-Young
FY
Lee
Shou-Dong
SD
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
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