Atrial natriuretic factor in experimental cirrhosis in rats.

Atrial natriuretic factor (ANF) is a cardiac hormone with potent natriuretic, diuretic, and vasorelaxant properties. Although abnormalities in ANF release, plasma level, and renal receptors have been described in humans and/or animals with cirrhosis and ascites, little is known about the ANF hormonal system in cirrhosis without ascites. The aim of this study was to examine the ANF hormonal system in an animal model of cirrhosis to determine whether compensated cirrhosis is associated with changes in the ANF hormonal system. Pair-fed rats were studied 5-7 weeks after either sham surgery or bile duct ligation. Bile duct-ligated (BDL) rats had elevated portal pressure and cirrhosis but did not have ascites. ANF messenger RNA levels were increased onefold in the atria of BDL rats. Sham-operated and BDL rats had similar plasma ANF levels. Competitive binding inhibition studies of isolated glomeruli showed a single class of receptors in sham-operated and BDL rats. The equilibrium dissociation constant was similar in sham-operated (0.51 nmol/L) and BDL (0.63 nmol/L) rats. Glomerular ANF receptor density increased significantly in BDL rats. Cyclic guanosine monophosphate generation in isolated glomeruli in response to 100 nmol/L ANF decreased slightly but not significantly in BDL rats. It was concluded that the ANF hormonal system is altered in cirrhosis without ascites; atrial messenger RNA level and glomerular ANF receptor density are increased.

Atrial natriuretic peptide in portal vein-ligated rats: alterations in cardiac production, plasma level and glomerular receptor density and affinity.

The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of portal hypertension on indomethacin-induced small intestinal ulceration in the rat.

The purpose of this study was to determine whether portal hypertension potentiates intestinal ulceration induced by indomethacin. Portal hypertension was produced in male Sprague-Dawley rats by two-staged ligation of the portal vein. Sham-operated rats were used as controls. The rats were given 20 mg/kg of indomethacin intragastrically, 7 and 14 days, respectively, after complete portal vein ligation. Forty-eight and 72 h after indomethacin, portal pressures were measured and the whole small intestine removed for quantitative measurement of the percent of the mucosa ulcerated by computerized image analysis. There were no differences in the area of ulceration between the portal hypertensive and sham-operated rats at either 7 or 14 days, despite the presence of significant portal hypertension. Portal hypertension does not appear to potentiate small intestinal ulceration induced by indomethacin in rats.

Diagnosis and hemodynamic assessment of portal hypertension.

Rational treatment of portal hypertensive complications requires a knowledge of the cause of portal hypertension and an assessment of the severity of liver disease. In the United States, chronic liver disease, usually due to alcohol, is the most common underlying cause. The history, physical examination, and laboratory analysis are usually sufficient to confirm the presence of underlying liver disease. If there is any question as to the etiology of portal hypertension, however, a more complete evaluation is required, whether the presenting complication is ascites, variceal bleeding, or hypersplenism. Usually, such an evaluation will require a liver biopsy, portal pressure measurement, and angiography. Occasionally, a noninvasive evaluation will be sufficient, but the value of these noninvasive parameters is still under investigation. Surgical mortality generally depends on the severity of the liver disease. Therefore, surgical intervention must be carefully considered in comparison to other therapeutic modalities depending on the patient's hepatic functional reserve. Secondary bacterial peritonitis due to perforation requires surgery regardless of the severity of the underlying liver disease.