Gastroenterology

Gastroenterology

Volume 109, Issue 5, November 1995, Pages 1624-1630
Gastroenterology

Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats,☆☆

https://doi.org/10.1016/0016-5085(95)90652-5Get rights and content

Abstract

Background & Aims Recent studies suggest that production of nitric oxide is increased in cirrhosis. This study determines to what extent this increased production contributes to arterial vasodilation and hyperdynamic circulation in cirrhosis. Methods Mean arterial pressure (MAP), cardiac index, and Systemic vascular resistance (SVR) were determined in cirrhotic rats with ascites undergoing long-term treatment with different doses of the NO synthesis inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (3 mg or 0.5 mg. kg−1 · day−1). Untreated cirrhotic rats with ascites and controls were also studied. The vascular production of NO was estimated by the aortic concentration of guanosine 3′,5′-cyclic monophosphate (cGMP). Results Untreated cirrhotic rats had significantly lower MAP and SVR and higher cardiac index and aortic cGMP concentration than controls. When administrated to cirrhotic rats, an l-NAME dose of 3 mg · kg−1 · day−1 induced a reduction of cGMP concentration less than normal levels. In these rats, MAP and SVR increased to greater than and cardiac index decreased to less than values in controls. By contrast, cirrhotic rats treated with 0.5 mg · kg−1 · day−1 l-NAME had similar aortic cGMP concentrations as controls, suggesting a normalization of NO production. This was associated with a normalization of MAP, cardiac index, and SVR and a reduction in the elevated plasma renin activity and vasopressin concentration. Conclusions Normalization of vascular NO production corrects systemic hemodynamic abnormalities in cirrhotic rats with ascites.

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    Supported by grant DK 19928 from the National Institutes of Health. Dr. Niederberger received a grant from the Swiss National Science Foundation. Dr. Ginès received grant CIRIT BE 93-148 from the Consell Interdepartmental de Recerca i Innovació Tecnològica, Generalitat de Catalunya, Catalunya, Spain, and a grant from the Asociación Española para el Estudio del Hígado. Dr. Martin received a grant from the University Hospital of Geneva, Geneva, Switzerland.

    ☆☆

    Presented in part at the 27th annual meeting of the American Society of Nephrology on October 26–27, 1994, and published in abstract form (J Am Soc Nephrol 1994;5:585A).

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