AJP - Regulatory, Integrative and Comparative Physiology, Vol 243, Issue 5 491-R499, Copyright © 1982 by American Physiological Society
Oral antidiuretic therapy: studies in the diabetes insipidus rat
L. B. Kinter and R. Beeuwkes 3rd
In hypothalamic diabetes insipidus, water balance is achieved primarily
through the thirst mechanism. The administration of an antidiuretic agent
in the drinking water should restore the antidiuretic response to volume
and osmoregulatory drive. To test this hypothesis, homozygous Brattleboro
strain rats were given arginine vasopressin (AVP) or
1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in
concentrations of 10-10,000 micrograms/l (AVP) and 5-10,000 micrograms/l
(dDAVP). Oral AVP was found to be ineffective. Oral dDAVP resulted in 1) a
progressive increase in dDAVP dose, from 2.3 to 2,559
micrograms.day-1.kg-1; 2) a dose-dependent increase in urine osmolality
from 306 to 1,796 mosmol/kg; and 3) a dose-dependent decrease in urinary
solute excretion. At each dDAVP dose level, stable physiological states
were achieved within 24 h. Similar antidiuretic states were achieved when
dDAVP was administered in increasing doses or when therapy was initiated at
a high dose. These findings demonstrate that inclusion of an appropriate
antidiuretic agent in the drinking water can restore the renal response to
volume-osmoregulatory drive.
