Fate and excretion of the pressor activity of vasopressin in rats

Abstract

The fate of the antidiuretic activity of vasopressin has been investigated in experiments in vivo (Burn & Singh Grewal, 1951;Heller, 1952Heller, , 1953Ginsburg & Heller, 1953;Dicker, 1954;Dicker & Greenbaum, 1954) and in experiments in vitro (Heller & Urban, 1935;Birnie, 1953;Dicker & Greenbaum, 1956). The antidiuretic activity of vasopressin appears to be inactivated by both liver and kidneys though the manner in which the inactivation takes place is still not clear. As for the metabolism of the pressor activity of vasopressin, little is known about its fate in the body beyond the fact that the pressor activity of post-pituitary gland extracts appears to be less stable than the antidiuretic activity (Heller, 1939).Since vasopressin has been synthesized there can be no doubt that both activities belong to the same octapeptide molecule. According to van Dyke (1955) the pharmacological activities of the vasopressin are abolished by cleavage of the disulphide bond. As, however, the two activities of vasopressin are so different, there is a possibility that the metabolism and the rate of excretion of the pressor activity are different from those of the antidiuretic activity. The present investigation is a contribution to this problem. METHODSMale albino rats of approximately 250 g were used. They had been bred and reared in the Department's animal house and fed on a standard diet containing: protein 14 g, fat 4 g, and soluble carbohydrate 49 g/100 g.The pressor activity was assayed on rats injected with urethane and dibenamine (Dekanski, 1952). The errors of the method fell within the limits stated previously (Dicker & Nunn, 1957). Nephrectomy and evisceration were performed on rats under ethanol anaesthesia, induced by the administration of 5 ml./100 g of a 12% (v/v) ethanol solution, and maintained, if necessary, by intravenous injections of 1 ml. of a 10% ethanol solution. The 'evisceration' consisted in the removal of the whole of the gastro-intestinal tract with the pancreas and spleen: in what follows the word is used with this special meaning. The liver, however, remained in 8itu, but its whole blood supply, except that from the vena cava, was stopped by ligation of the coeliac and the superior mesenteric arteries and their branches, and of the portal vein and its branches.

Antidiuretic Activity in the Fetal and Newborn Rabbit Hypophysis

“…Thus, in newborn rats deprived of milk for 24 h, the quantity of hypophysial ADH decreases (17). This is not the case for adult rats deprived of water for 4 days (13). In addition, in adult rabbits, a hypophysial ADH depletion of 30 % appears only after 7 days of water deprivation (24).…”

The destruction of the antidiuretic activity of vasopressin by —SH active compounds

“…Several years ago Heller (1939) had already noted a difference between the stability of both pressor and antidiuretic activities. A difference in the metabolism of the antidiuretic and the pressor activities of Pitressin injected in vivo has also been postulated more recently by Dicker & Nunn (1957). In a pilot experiment, during which vasopressin had been incubated with cysteine and assayed simultaneously for its antidiuretic and pressor activities, it was found that while there was no decrease of the pressor activity, the antidiuretic activity was reduced by one third.…”

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

“…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.…”