Chronic inhibition of nitric oxide increases the collateral vascular responsiveness to vasopressin in portal hypertensive rats.
OBJECTIVE
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 (approximately 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.
Huang
Hui-Chun
HC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, No. 201, Sec 2, Shih-Pai Road, Taipei 11217, Taiwan
Wang
Sun-Sang
SS
Chan
Che-Chang
CC
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chih
MC
Tai
Chun-Ching
CC
Lai
I-Nien
IN
Lee
Shou-Dong
SD
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D008026:Ligation; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester