Elsevier

Hepatology

Volume 21, Issue 6, June 1995, Pages 1625-1631
Hepatology

Increased aortic cyclic guanosine monophosphate concentration in experimental cirrhosis in rats: Evidence for a role of nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis

https://doi.org/10.1016/0270-9139(95)90468-9Get rights and content

Abstract

Arterial vasodilation is considered to be the key factor in the development of sodium and water retention leading to ascites formation in cirrhosis. To determine if nitric oxide (NO) is involved in the pathogenesis of arterial vasodilation in cirrhosis, we measured the concentration of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride-induced cirrhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 ± 70; no ascites, 597 ± 48; controls, 331 ± 25 fmol/mg, ANOVA F = 23.1, P < .0001), and correlated inversely with arterial pressure (r = −.56, P < .0001) and systemic vascular resistance (r = −.69, P = .014) and directly with cardiac index (r = .74, P < .01). The chronic administration of the NO synthesis inhibitor NG-nitro-l-arginine-methylester (l-NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP concentration in cirrhotic rats with ascites to similar values obtained in l-NAME-treated control rats (86 ± 14 vs. 89 ± 8 fmol/mg, respectively, NS), indicating that the high-aortic cGMP content in cirrhotic rats was caused by an increased NO synthesis. Mean arterial pressure after l-NAME treatment increased to similar values in both groups of animals. These results suggest that in cirrhosis there is an increased vascular production of NO that may play a role in the pathogenesis of arterial vasodilation.

References (45)

  • J Bosch et al.

    Hepatic, splanchnic and systemic haemodynamic abnormalities in portal hypertension

  • I Fleming et al.

    Incubation with endotoxin activates the L-arginine pathway in vascular tissue

    Biochem Biophys Res Commun

    (1990)
  • V Arroyo et al.

    Ascites, renal failure, and electrolyte disorders in cirrhosis

  • V Arroyo et al.

    Effect of angiotensin-II blockade on systemic and hepatic haemodynamics and on the renin-angiotensin-aldosterone system in cirrhosis with ascites

    Eur J Clin Invest

    (1981)
  • KM Nicholls et al.

    Sodium excretion in advanced cirrhosis: effect of expansion of central blood volume and suppression of plasma aldosterone

    Hepatology

    (1986)
  • C Lopez et al.

    Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride—induced cirrhosis

    Hepatology

    (1991)
  • RW Schrier

    Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (1)

    N Engl J Med

    (1988)
  • RW Schrier

    Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2)

    N Engl J Med

    (1988)
  • RW Schrier et al.

    Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis

    Hepatology

    (1988)
  • RM Palmer et al.

    Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

    Nature

    (1987)
  • RM Palmer et al.

    Vascular endothelial cells synthesize nitric oxide from L-arginine

    Nature

    (1988)
  • S Moncada et al.

    Nitric oxide: physiology, pathophysiology, and pharmacology

    Pharmacol Rev

    (1991)
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    Supported by a grant from the National Institutes of Health (DK 19928) Bethesda, MD. MN received a grant from the Swiss National Science Foundation. PG received grants from the Dirección General de Investigación y Técnica (DGICYT 92–317) and the Asociación Española para el Estudio del Higado. P-YM received a grant from the University Hospital of Geneva, Geneva, Switzerland.

    1

    Dr Niederberger and Dr Ginès were affiliated with the Department of Medicine, University of Colorado School of Medicine when the research presented in this article was conducted.

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