Oral antidiuretic therapy: studies in the diabetes insipidus rat

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Abstract
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 rats were given arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in concentrations of 10-10,000 .mu.g/l (AVP) and 5-10,000 .mu.g/l (dDAVP). Oral AVP was ineffective. Oral dDAVP resulted in a progressive increase in dDAVP dose, from 2.3 to 2559 .mu.g .cntdot. day-1 .cntdot. kg-1; a dose-dependent increase in urine osmolality from 306 to 1796 mosmol/kg; and 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. Inclusion of an appropriate antidiuretic agent in the drinking water apparently can restore the renal response to volume-osmoregulatory drive.

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