Abstract

The effects of prolonged administration of vasopressin on plasma sodium and on renal electrolyte excretion, concentrating capacity, excretion of water load, glomerular filtration rate and renal plasma flow were studied in three trained dogs. In six experiments, vasopressin was administered daily for 28 days. The dietary intakes of electrolytes were kept constant. Water intake was allowed ad libitum. The dogs developed hyponatremia, hemodilution (low plasma osmolality) and renal sodium loss, findings which are characteristic in patients with Syndrome of Inappropriate Secretion of Antidiuretic Hormone. Since water balance was maintained, it is concluded that vasopressin has an "intrinsic" natriuretic activity independent of water retention. However, our data also suggest that the fall in plasma sodium could not be entirely related to the natriuretic effect of vasopressin. It was also found that in the absence of overhydration, escape from the antidiuretic effect of vasopressin could not be demonstrated. When a water load was given to the dogs on the 25th day on vasopressin, none of the dogs was able to excrete the water load. Our observations suggest that the loss of response to vasopressin after prolonged administration of the hormone and water load is not due to a development of tolerance or a loss of renal receptor sensitivity to vasopressin, but probably can be explained in terms of dilution of medullary osmotic gradient or other change(s) evoked by overhydration.