Vasopressin response and shunting modulation in cirrhotic rats by chronic nitric oxide inhibition.
OBJECTIVE
Nitric oxide (NO) plays a significant role in the vascular hyposensitivity to vasoconstrictors in cirrhosis. Chronic NO inhibition improves the portal-systemic collateral responsiveness to arginine(8)-vasopressin (AVP) and ameliorates shunting degree in rats with prehepatic portal hypertension. This study investigated whether long-term NO inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) enhances the collateral vascular responsiveness to AVP and alleviates the severity of shunting in cirrhotic rats.


METHODS
Bile duct-ligated (BDL) rats received L-NAME in tap water (25 mg/kg/day) or tap water only (control) for 1 week from the 36th day after BDL. On the 43rd day, the mean arterial pressure and portal pressure were measured. With an in situ perfusion model of portal-systemic collateral vasculature, different concentrations of AVP (10(-10)-10(-7) mol/L) with a constant flow rate (12 mL/min) were applied to assess the perfusion pressure changes of collaterals. In addition, flow pressure curves were obtained with different flow rates (6-18 mL/min): the slopes serve as indices of collateral vascular resistance and the higher resistance indicates less collateral.


RESULTS
The mean arterial pressure was significantly increased after L-NAME treatment (P < 0.05), whereas the heart rate and portal pressure were not significantly modified. As compared with the controls, the L-NAME group exerted significantly higher perfusion pressure changes to AVP at the concentrations of 3 x 10(-8), 10(-7) and 3 x 10(-7) mol/L. In addition, chronic L-NAME administration induced collateral vascular resistance elevation, suggesting the attenuation of portal-systemic shunting.


CONCLUSIONS
Chronic NO inhibition improves the collateral vascular responsiveness to AVP and ameliorates portal-systemic shunting in BDL cirrhotic rats.
Huang
Hui-Chun
HC
Department of Medicine, Division of Gastroenterology, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan.
Wang
Sun-Sang
SS
Lee
Fa-Yauh
FY
Chang
Ching-Chih
CC
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chih
MC
Lee
Shou-Dong
SD
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects*; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D008099:Liver / Q000201:enzymology* / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D004791:Enzyme Inhibitors; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester