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Vasopressin response and shunting modulation in cirrhotic rats by chronic nitric oxide inhibition
Author(s) -
Huang HuiChun,
Wang SunSang,
Lee FaYauh,
Chang ChingChih,
Chang FullYoung,
Lin HanChieh,
Hou MingChih,
Lee ShouDong
Publication year - 2008
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2007.05122.x
Subject(s) - vasopressin , medicine , portal hypertension , portal venous pressure , hyperdynamic circulation , vascular resistance , endocrinology , nitric oxide , blood pressure , perfusion , cirrhosis , cardiology , mean arterial pressure , collateral circulation , heart rate
Background and Aim: 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 × 10 −8 , 10 −7 and 3 × 10 −7 mol/L. In addition, chronic L‐NAME administration induced collateral vascular resistance elevation, suggesting the attenuation of portal‐systemic shunting. Conclusion: Chronic NO inhibition improves the collateral vascular responsiveness to AVP and ameliorates portal‐systemic shunting in BDL cirrhotic rats.