Circulation Research, Vol 53, 794-804, Copyright © 1983 by American Heart Association

ARTICLES

Mechanisms of escape from desmopressin in the rat

PA Gross, JK Kim and RJ Anderson

The mechanism(s) of renal escape from the hydro-osmotic effect of vasopressin is unknown. We therefore studied escape in conscious, unrestrained rats receiving continuous intravascular infusions of 1- deamino-8-arginine-vasopressin (desmopressin) and hypotonic fluid over 5 days. Escape from desmopressin started 8 hours after exposure and was characterized by a progressive increase in urine flow and decreases in urine osmolality and free water reabsorption. When positive water balance was prevented by matching the rate of infusion of hypotonic fluid to urine flow while maintaining the dose of desmopressin constant, escape did not occur. This suggested that water retention, rather than chronic exposure to desmopressin, mediated the escape. To elucidate the mechanism whereby water retention induces escape from desmopressin, urinary prostaglandin E2 excretion was measured and found to be increased concomitant with the onset of escape. Prevention of this increase in urinary prostaglandin E2 excretion with indomethacin resulted in additional water retention and a delay in the onset of escape. During the maintenance of escape, after significant water retention occurred, increases in mean arterial pressure, renal blood flow, and glomerular filtration rate were observed. Renal interstitial solute concentration remained constant through escape. Basal and vasopressin-stimulated collecting tubular and thick ascending limb adenylate cyclase did not differ when control and escape animals were compared. These results suggest that enhanced renal synthesis of prostaglandin E2 facilitates the early phase of escape; later, water retention results in plasma volume expansion with increases in cardiac index, arterial pressure, renal blood flow, and glomerular filtration rate. These systemic and renal hemodynamic alterations may be important in maintaining escape from desmopressin.

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