Abstract
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.
Keywords
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References
- Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model.Am J Physiol. 1985; 248: G618-G625
- The effect of continuous vasopressin infusion on splanchnic blood flow, liver function, and portal and central venous pressures in patients with cirrhosis.Scand J Clin Lab Invest. 1984; 44: 251-256
- Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension.Gut. 1988; 29: 372-377
- Hemodynamic changes of systemic, hepatic and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis.Dig Dis Sci. 1988; 33: 1103-1109
- Effects of vasopressin on portal-systemic collaterals in portal hypertensive rats: role of nitric oxide and prostaglandin.Hepatology. 1999; 30: 630-635
- Hyperdynamic circulation in cirrhosis: a role for nitric oxide?.Lancet. 1991; 337: 776-778
- The nitric oxide hypothesis and the hyperdynamic circulation in cirrhosis.Hepatology. 1994; 29: 1343-1350
- Decreased mesenteric vascular response to angiotensin II in portal hypertension.J Surg Res. 1990; 48: 341-344
- The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats.Hepatology. 1992; 16: 1043-1048
- Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide.Proc Natl Acad Sci USA. 1993; 90: 267-271
- Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension.Eur J Pharmacol. 1996; 312: 63-68
- Nitric oxide-dependent and -independent vascular hyporeactivity in mesenteric arteries of portal hypertensive rats.Br J Pharmacol. 1997; 24: 739-746
- Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats.Gastroenterology. 1992; 103: 235-239
- Measurement of the portal-systemic shunting in the rat by using γ-labeled microspheres.Am J Physiol. 1981; 240: G371-G375
- Pharmacology of portal-systemic collaterals in portal hypertensive rats: role of the endothelium.Am J Physiol. 1992; 263: G544-G550
- A simple and inexpensive membrane ‘lung’ for small organ perfusions.J Lipid Res. 1974; 15: 182-186
- Administration of Nω-nitro-l-arginine ameliorates portal-systemic shunting in poral-hypertensive rats.Gastroenterology. 1993; 105: 1464-1470
- Aminoguanidine corrects hyperdynamic circulation without ameliorating portal hypertension and portal hypertensive gastropathy in anesthetized portal hypertensive rats.J Hepatol. 1997; 26: 687-693
- Effects of long-term octreotide treatment on the response of portal-systemic collaterals to Vasopressin in portal hypertensive rats.Eur J Clin Invest. 2002; 32: 316-321
- Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells.J Clin Invest. 1997; 100: 3131-3139
- Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-α.Am J Pathol. 1997; 151: 557-563
- Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P.J Clin Invest. 1994; 94: 2036-2044
- Increased angiogenesis in portal hypertensive rats: role of nitric oxide.Hepatology. 1999; 29: 1044-1049
- In vivo angiogenesis in normal and portal hypertensive rats: role of basic fibroblast growth factor and nitric oxide.J Hepatol. 2001; 34: 644-650
- Portal hypertension ameliorates arterial hypertension in spontaneously hypertensive rats.J Hepatol. 1989; 8: 294-301
- Liver cirrhosis.Hepatology. 1982; 2: 892-894
- Regional differences in the arterial response to vasopressin: role of endothelial nitric oxide.Br J Pharmacol. 1996; 118: 1848-1854
- The treatment of portal hypertension: a meta-analytic review.Hepatology. 1995; 22: 332-354
- Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals.Circ Res. 1986; 59: 133-142
- Measurement of azygous venous blood flow in the evaluation of portal hypertension in patients with cirrhosis: clinical and haemodynamic correlations in 100 patients.J Hepatol. 1985; 1: 125-139
- Responses of femoral resistance vessels to angiotensin in vitro.Eur J Pharmacol. 1987; 135: 61-68
- Nω-amino-l-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin.J Exp Med. 1992; 176: 1175-1182
- Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.Lancet. 1991; 338: 1557-1558
Article info
Publication history
Accepted:
October 8,
2003
Received in revised form:
September 24,
2003
Received:
May 21,
2003
Identification
Copyright
© 2003 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
