Vasopressin response and shunting modulation in cirrhotic rats by chronic nitric oxide inhibition

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.