VASOPRESSIN RELEASE AND WATER METABOLISM IN PATIENTS WITH CIRRHOSIS

Water retention is a complication in many patients with cirrhosis, usu ally attributed to excessive release of arginine vasopressin. To inves tigate the responsiveness of arginine vasopressin to osmotic and non-o smotic stimuli and its relationship to free water excretion, we studie d 19 patients with cirrhosis under three different conditions: 45 min with legs raised to 60 degrees, to expand the central blood volume; in fusion of 1000 ml of 0.45% saline solution to reduce plasma osmolality ; and rapid injection of 50 ml of 2 M NaCl to increase plasma osmolali ty. Both expansion of central blood volume and decrease of plasma osmo lality significantly reduced plasma vasopressin levels (from 2.1+/-0.6 to 1.39+/-0.3 pg/ml, p<0.04; and from 1.09+/-0.25 to 0.41+/-0.13 pg/m l, p<0.0001). The changes in free water excretion differentiated two s ubgroups of patients during each test: excretors and non-excretors. In the excretors, increased free water excretion was associated with sup pressed vasopressin levels (below 0.5 pg/ml) and normal renal function . In the non-excretors, inability to improve free water excretion was associated with high vasopressin levels or with reduced distal deliver y of the glomerular filtrate, except in some cases where vasopressin l evels had fallen below 0.5 pg/ml and renal function was normal. For th ese cases the presence of other vasopressin-independent antidiuretic m echanisms is conceivable. The injection of hypertonic saline solution caused significant rises in plasma osmolality (from 287+/-1.9 to 292+/ -1.6 mmol/kg, p<0.05) and in plasma vasopressin levels (from 1.13+/-0. 29 to 2.86+/-0.52 pg/ml, p<0.05). These results suggest that vasopress in release in patients with cirrhosis is normally responsive to osmoti c and non-osmotic stimuli, although our results show a lower theoretic al osmolar threshold for suppression of vasopressin release in non-exc retors than in excretors (276 vs 284 mmol/kg). (C) Journal of Hepatolo gy.