AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 6 1617-R1625, Copyright © 1994 by American Physiological Society
Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis
J. G. Verbalis
Department of Medicine, University of Pittsburgh, Pennsylvania 15261.
Rats were infused with a selective agonist of vasopressin V2 receptors
(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) hyponatremia.
Whole body water and electrolyte contents were analyzed after 1, 7, and 14
days of hyponatremia to assess the relative contributions from water
retention and sodium depletion to hyponatremia of varying duration and
severity. Body water of the hyponatremic rats was significantly 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 significantly different from
controls. Body Na+ and Cl- both decreased significantly after 1 day of
hyponatremia, and these decreases were sustained for 14 days; measured
decreases were significantly greater in the more 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 rats after 7 and 14 days. Analysis of the
measured plasma Na+ concentrations vs. those predicted by the changes in
body water and sodium showed that both water retention and sodium losses
were necessary to predict the final plasma [Na+]. However, the relative
contribution from each varied with the duration of induced hyponatremia:
acutely, water retention was the major cause of decreased plasma [Na+], but
sodium depletion became predominant with longer periods of sustained
hyponatremia.
