INCREASED PLASMA-LEVELS OF SUBSTANCE-P AND DISTURBED WATER-EXCRETION IN PATIENTS WITH LIVER-CIRRHOSIS

Background: The pathogenesis of impaired water excretion in liver cirr hosis has not been fully elucidated. Methods: We induced an intravenou s water overload of 20 ml/kg body weight in 10 cirrhotics without asci tes (CLC) 11 cirrhotics with ascites (DLC), and 10 normal subjects (N) and investigated the relationship of plasma levels of substance P (SP ), norepinephrine (NE), and antidiuretic hormone (ADH) to impaired wat er excretion. Results: Free water clearance (C-H2O) was lower in DLC ( mean, 2.7 ml/min) than in N (8.3 ml/min; P < 0.001) and CLC (6.9 ml/mi n; P < 0.001), In DLC the creatinine clearance (CCr) maximal urine flo w rate/CCr, (C-H2O + C-Na)/CCr, and mean arterial pressure (MAP) were significantly lower than in N and CLC. There was a progressive increas e in basal SP, from lowest in N to CLC, to highest in DLC. Basal NE in creased in CLC and DLC. Basal ADH did not differ among N, CLC, and DLC . In cirrhotics C-H2O was correlated positively with serum albumin and cholinesterase and negatively with the retention rate of indocyanine green at 15 min. Basal SP was negatively correlated with C-H2O (r= -0. 71; P < 0.001) and MAP (r= -0.56; P < 0.005). Basal NE was correlated positively with basal SP (r= 0.67, P < 0.01). Conclusions: Decreased C -H2O is closely related to the severity of the liver disturbance. Decr eased CCr and reduced delivery of filtrate to the ascending limb of th e loop of Henle secondary to an increased sodium reabsorption in the p roximal tubule may play an important role in the impairment of water e xcretion. The increase in SP, which has a potent vasodilatory action, and the associated enhanced activity of the sympathetic nervous system may be responsible for the mild or moderate impairment of water excre tion in the absence of nonosmotic hypersecretion of ADH in cirrhotics with ascites.