The Renal Clearance and Plasma Binding of Vasopressin in the Dog

Abstract

SUMMARY The isolated dog kidney was perfused with blood containing 1 m-u. arginine vasopressin/ml. In other experiments 40 or 50 m-u./min. were infused into three intact dogs. Antidiuretic activity was measured in renal venous blood, arterial blood, and in the urine. Renal blood flow was determined directly in the perfused dog kidney and by p-aminohippuric acid clearance in the intact dog; glomerular filtration rate was measured by either inulin or creatinine clearance. About 38% of the hormone was extracted from the arterial blood in its passage through the kidney. Of the total amount of hormone infused, about 18% was eliminated by each kidney. The quantity of vasopressin extracted from the blood was greater than that excreted in the urine, indicating that the hormone is inactivated by the kidney. In intact dogs, the amount of hormone filtered by the kidney was less than that excreted, suggesting tubular secretion. It was calculated that the release of endogenous arginine vasopressin induced by the stimuli of anaesthesia and surgery was between 3 and 7 m-u./min. and that approximately 15% of the endogenous hormone was excreted. Ultrafiltration of dog plasma at three different concentrations of arginine vasopressin (30, 100 and 290 μ-u./ml.) showed that binding was reduced as the concentration was raised and that at the concentration of hormone in the experiments, less than 30% was bound. The difficulties of relating these findings at artificially high blood concentrations to those at physiological blood concentrations of vasopressin are discussed.

Distribution, blood transport, and degradation of antidiuretic hormone in man.

“…Finally, the presence of inhibitors and interfering compounds in unextracted urine or plasma must always be kept in mind when evaluating bioassay data. From the present data we conclude that ADH is eliminated principally by glomerular filtration at physiological concentration, as previously reported in dogs (31), rats (32), and rabbits (33). Renal clearance expressed as percentage of MCR in our subjects, excluding the one with unexplained low renal clearance, averaged 27%.…”

A sensitive and specific assay for vasopressin in the circulating blood

“…Harvey, Jones & Lee (1967) found vasopressin to be bound to plasma protein, but this process would presumably be too rapid to be detected by our technique.…”

Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs

“…Since plasma AVP levels remained above the basal value during the entire post-injection period and in view of the fact that the plasma half-fife of AVP is relatively short (Lauson, 1974), the continuous release of AVP over the 2 h test period should be considered. Furthermore various reports on metabolic clearance of AVP (Harvey et al, 1967;Matsui et al, 1983;Share et al, 1985) rule out the possibility of a decreased metabolic clearance rate with high plasma AVP levels.…”