Background/Aims: Nitric oxide (NO), a potent vasodilator, plays a significant role in the vascular hyposensitivity to vasoconstrictors related to portal hypertension. Chronic NO inhibition ameliorates portal-systemic collaterals in portal hypertensive rats. This study investigated whether chronic NO inhibition by NG-nitro-l-arginine methyl ester (L-NAME) improves the portal-systemic collateral vascular responsiveness to arginine vasopressin (AVP) in portal hypertensive rats.
Methods: Partially portal vein-ligated (PVL) rats received L-NAME in tap water (∼25 mg/kg per day) or tap water only (control) since 2 days prior to until 7 days after PVL. Mean arterial pressure was measured on the 8th day. By in situ perfusion model, different concentrations of AVP (10−10–10−7 M) with a constant flow rate (20 ml/min) were applied to assess the perfusion pressure of collateral vessels. In another series, perfusion with different flow rates (5–30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances and higher resistances indicate less collaterals.
Results: Mean arterial pressure was higher in the L-NAME-treated group than that of the control group (P<0.05). As compared with the controls, L-NAME-treated rats achieved significantly higher perfusion pressures in response to AVP. In addition, chronic L-NAME treatment also induced an increase of collateral vascular resistance, suggesting the attenuation of portal-systemic shunting.
Conclusions: Chronic NO inhibition ameliorates portal-systemic shunting and improves the collateral vascular responsiveness to AVP in portal hypertensive rats.
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Accepted: October 8, 2003
Received in revised form: September 24, 2003
Received: May 21, 2003
© 2003 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.