PATHOGENESIS OF HYPONATREMIA IN AN EXPERIMENTAL-MODEL OF THE SYNDROMEOF INAPPROPRIATE ANTIDIURESIS

Rats were infused with a selective agonist of vasopressin V-2 receptor s (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyp onatremia. Whole body water and electrolyte contents were analyzed aft er 1, 7, and 14 days of hyponatremia to assess the relative contributi ons from water retention and sodium depletion to hyponatremia of varyi ng duration and severity. Body water of the hyponatremic rats was sign ificantly increased over normonatremic control rats after 1 and 7 days ; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not signif icantly different from controls. Body Na+ and Cl- both decreased signi ficantly after 1 day of hyponatremia, and these decreases were sustain ed for 14 days; measured decreases were significantly greater in the m ore hyponatremic rats compared with the less hyponatremic rats. Body K + of the 1 ng/h DDAVP-infused rats was not different from control rats , but significant K+ decreases occurred in the 5 ng/h DDAVP-infused ra ts after 7 and 14 days. Analysis of the measured plasma Na+ concentrat ions vs. those predicted by the changes in body water and sodium showe d that both water retention and sodium losses were necessary to predic t the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water rete ntion was the major cause of decreased plasma [Na+], but sodium deplet ion became predominant with longer periods of sustained hyponatremia.