PLASMA-LEVELS OF SUBSTANCE-P IN LIVER-CIRRHOSIS - RELATIONSHIP TO THEACTIVATION OF VASOPRESSOR SYSTEMS AND URINARY SODIUM-EXCRETION

The mediators of the hyperdynamic circulation of liver cirrhosis are n ot well characterized. Substance P is a potent vasodilatory peptide pr oduced by the enteric nervous system and partly cleared by the Liver. In this work we have investigated the plasma levels of substance P and their relationship to the hemodynamic, neurohormonal, and renal funct ion changes occurring in patients with cirrhosis. Seven healthy subjec ts (control group), 7 cirrhotic patients without ascites (group I), an d 24 cirrhotic patients with ascites (group II) were studied. Cardiac output (CO), femoral blood how (FBF), blood volume (BV), femoral arter iovenous difference of oxygen content (Ca-v O-2), plasma renin activit y (PRA), plasma aldosterone concentration (PAC), and plasma norepineph rine (NE) were determined. Five patients underwent trans-jugular intra hepatic porto-systemic stent shunt (TIPSS) because of refractory ascit es. Immunoreactive substance P (irSP) was measured by radioimmunoassay after plasma extraction, irSP was higher in ascitic patients than in healthy controls (P < .01) and directly correlated with PRA, PAC, plas ma NE, and Pugh's score and was inversely correlated with urinary sodi um excretion, glomerular filtration rate, and Ca-v O-2, No differences were observed between portal and peripheral vein irSP concentration. TIPSS placement induced a decrease in portal pressure and an increase in CO but circulating irSP remained unchanged, Our data show that circ ulating irSP is increased in decompensated cirrhotic patients and may be involved in the pathogenesis of the hemodynamic changes of cirrhosi s. Alleviation of portal hypertension did not result in decreased plas ma levels of this vasodilatory substance.