THE METABOLISM OF EXOGENOUS AND ENDOGENOUS ANTIDIURETIC HORMONE IN THE KIDNEY AND LIVER IN VIVO

Abstract

Negligible antidiuretic activity (less than 0.17 mU./g.) was found in extracts of the kidneys either of unanaesthetized adult rats in normal water balance or of rats in whose blood a rise of the level of endogenous antidiuretic hormone had been induced by ether anaesthesia. Extracts of the livers of unanaesthetized rats had negligible antidiuretic activity (less than 0.06 mU./g.),but liver extracts from rats anaesthetized with ether showed antidiuretic effects equivalent to 0.74 ±0.24 mU. Pitressin/g. liver. When Pitressin was injected intravenously into unanaesthetized rats, small amounts of antidiuretic activity were occasionally found in the livers and the kidneys of animals killed up to 3 mmn. after the injection but none in animals killed later. Some 3% of the antidiuretic activity of an injected dose of Pitressin was found in the urine and the " dead space" of the kidneys in rats decapitated 3 min. after the intravenous injection. When Pitressin was added to rat kidney homogenate and the mixture was incubated at 380, only 0.75% of the initial antidiuretic activity was recovered after 30 min. and less than 0.40% after 60 min. Experiments with " glomerular " and " tubular " fractions of rat kidney indicated that the inactivation was essentially due to tubular tissue. It is suggested that, in the rat, the kidneys and perhaps the liver are not only sites of clearance of the antidiuretic hormone but also sites of irreversible inactivation. Ginsburg and Heller (1953a) and Crawford and Pinkham (1954) showed that, after intravenous injection into intact rats, the antidiuretic activity of doses of Pitressin (Parke Davis) ranging from 5 to 100 mU. /100 g. body weight disappeared rapidly from the circulation: 5 min. after the injection less than 5% of the injected antidiuretic activity could be recovered from the blood. Similar experiments were done by Dicker (1954), who infused rats with pitressin at rates ranging from 30 to 100 1MU. /min. / 100 g. In 4 of his animals, killed 2 to 3 min. after the end of the infusion, no antidiuretic activity could be demonstrated in the plasma; in two others the recovery was equivalent to about 1 % of the infused dose. However, when pitressin was injected or infused into nephrectomized rats (Ginsburg and Heller, 1953a;Crawford and Pinkham, 1954;Dicker, 1954), it was found that the antidiuretic activity was " cleared " at a considerably lower rate, the recovery after 2 to 5 min. varying from 37 to 63 % of the administered dose. Sham-nephrectomized rats (Crawford and Pinkham, 1954) or animals with both ureters tied (Dicker, 1954) cleared the antidiuretic hormone at about the same rate as intact rats. It seems therefore that the kidney of the rat plays an important role in the removal of antidiuretic hormone from the circulation. But it is not the only organ so concerned. Ginsburg and Heller (1953a) found also that considerable amounts of the antidiuretic principle were removed in the splanchnic vascular bed, and Ginsburg (1957) subsequently found that little or no pressor activity wa...

Antidiuretic Hormone Content of the Hypothalamo-Neurohypophysial System and Urinary Excretion of Antidiuretic Hormone in Rats During the Development of Diabetes Insipidus After Lesions in the Pituitary Stalk

“…In the rat smaller amounts of AD-activity are recovered from the urine after admini¬ stration of the hormone than in human beings or dogs. However, in the present experiments larger amounts of vasopressin were administered than in Heller's laboratory (Ginsburg & Heller, 1953;Heller & Zaidi, 1957). The present experiments show that in nearly all instances less than 1 % of AD-activity was recovered from 24-hr.…”

“…Vasopressin injected intravenously disappears rapidly from the blood (O'Connor, 1951;Dicker & Nunn, 1957;Heller & Zaidi, 1957). When 1 unit LVP was admini¬ stered subcutaneously, an amount approximately equivalent to that discharged by the posterior pituitary after stalk lesion, almost no influence on water intake and urine output was seen.…”

“…Reports on the urinary excretion of ADH in rats (Ginsburg & Heller, 1953;Heller & Zaidi, 1957;Sawyer, 1958), man (Cline, Cole & Holden, 1953;Noble & Taylor, 1953;Eisen & Lewis, 1954), dogs (Heller & Urban, 1935;Hare, Hickey & Hare, 1941 ;O'Connor, 1951 ;Thorn & Smith, 1965) and rabbits (Heller, 1937) are relatively scarce. In the rat smaller amounts of AD-activity are recovered from the urine after admini¬ stration of the hormone than in human beings or dogs.…”

The distribution of proteins that bind neurohypophysial hormones

“…More recently, it has been shown that the antidiuretic activity of serum, in rats stimulated by the intracarotid injection of hypertonic saline (Thorn & Silver, 1957) as well as exogenous hormone added to serum taken from rats under ethanol anaesthesia and therefore free from detectable endogenous hormone (Thorn, 1959), moved together with the fl-globulin fraction on electrophoresis; when eluted, the hormonal activities were not ultrafiltrable. Homogenates of kidney (Dicker & Greenbaum, 1956;Heller & Zaida, 1957), liver (Heller & Urban, 1935;Birnie, 1953), mammary gland (Werle & Maier, 1954), myometrium (Sawyer, 1954;Audrian & Clauser, 1960), spleen (Christlieb, 1940), as well as cell-free extracts of liver, kidney & spleen (Heller & Urban, 1935;Miller & Townsend, 1954) have been shown to cause inactivation of neurohypophysial hormones. In most of these studies however no clear distinctions were drawn between reversible binding of the hormone and irreversible enzymatic inactivation.…”

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

“…( 20) indicates that ADH secretion increases if PV decreases and/or [Na + ] increases [54]. The coefficients 0.27 and 0.73 come from the notion that ADH is excreted in the kidneys (27%; proportional to GFR [58]) and the liver (73%; proportional to hepatic blood flow, and therefore, approximately to PV [59]).…”