Adaptive responses to sustained volume expansion in hyponatraemic rats

Studies were carried out to evaluate adaptive responses to water retention in an experimental model of the syndrome of inappropriate antidiuresis (SIAD). Hyponatraemia was induced by continuous s.c. infusions of the antidiuretic vasopressin analogue 1-deamino-[8-D-arginine]-vasopressin in rats ingesting a 5% (w/v) dextrose solution. After 48 h of sustained decreases in the plasma concentration of Na+ to 23-25% of normal levels, all body fluid compartments were significantly expanded: plasma volume estimated by changes in plasma protein concentration was increased by 26%, extracellular fluid volume estimated by 22Na volume of distribution was increased by 24%, and total body water estimated by 3H2O volume of distribution was increased by 16%. Despite marked increases in all body fluid compartment volumes, mean arterial blood pressure was only modestly increased to 110 +/- 2 mmHg in conscious hyponatraemic rats. Consistent with the sustained volume expansion, both basal and stimulated plasma renin activities were significantly suppressed in the hyponatraemic rats. Plasma vasopressin levels were similarly suppressed, and the hyponatraemic rats showed a striking absence of endogenous vasopressin secretion in response to marked intravascular volume depletion (15-45%) produced by s.c. administration of polyethylene glycol. Plasma concentrations of atrial natriuretic peptide were initially stimulated four- to fivefold above basal levels in response to the water-induced volume expansion, but by 48 h fell to ranges not significantly different from basal unstimulated levels, despite continued plasma and extracellular fluid volume expansion at that time. These results illustrate that multiple haemodynamic and hormonal adaptive responses occur with sustained dilutional hyponatraemia in rats, and suggests that these can be of sufficient magnitude to allow continued water retention without necessarily provoking either escape from antidiuresis or continued natriuresis. In contrast with previous studies in experimental animals in which hyponatraemia was maintained by continuous forced administration of hypotonic fluid, rats in this model reached a steady state with characteristics resembling many of those observed clinically in patients with SIAD.