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

Hui Chun Huang, Sun Sang Wang, Fa Yauh Lee*, Ching Chih Chang, Full Young Chang, Han Chieh Lin, Ming Chih Hou, Shou Dong Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 NG-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.

Original languageEnglish
Pages (from-to)e265-e269
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume23
Issue number7 PT2
DOIs
StatePublished - Jul 2008

Keywords

  • Bile duct ligation
  • Cirrhosis
  • Nitric oxide
  • Portal-systemic collaterals
  • Vasopressin

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