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ADMINISTRATION of renin to rats pretreated with salt and desoxy-corticosterone (DCA), cortisone or 17-hydroxycorticosterone (cortisol) (1, 2, 3) elicits an eclampsia-like state associated with widespread acute destructive vascular lesions. This condition is attributable, in part, to the enhanced pressor effect of renin associated with the presence of excess adrenosteroids (4). Recently, a somewhat similar syndrome has been described in rats given thyroxin together with salt and DCA plus cortisone (5). In this situation the pressor and nephrosclerotic actions of thyroxine (6) may be additive to those of the steroids or it may act by specific sensitization of pressor mechanisms. The present experiments constitute a comparative study of the effects of thyroxine and renin in animals treated with adrenosteroids and also in animals with regenerating adrenals; the latter condition is stimulated by thyroxine (7) and is believed to be associated with hyperfunction or imbalance in steroid secretions (8).

Desoxycorticosterone acetate (DCA) corrects for some of the deficiencies caused by adrenalectomy. It also elicits functional and structural changes characteristic of hypertensive vascular disease (Selye et al., 1943; Masson et al., 1949). Its hormonal status in normal physiology is still in question. The possibility existed therefore that 17-hydroxy-11-desoxycorticosterone (compound “S”)which has been isolated a so from the adrenals, might be the most significant natural salt-retaining hormone. Existing data on the pharmaco ogical activities of this steroid are inadequate. Hence, we have compared the activity of its acetate with that of DCA under identical conditions in (1) adrenalectomized rats as well as in (2) rats under conditions used for the production of DCA hypertensive disease. 1. A drenalectomized rats. A. Experimental 28 rats weighing from 80 to 110 g. were adrenalectomized and divided equally into groups of 7. Group I consisted of untreated controls which received two daily injections of 0.1 c...

T TRINARY outputs of 17-ketosteroids (17-KS) and reducing (-R) or formaldehydogenic (F) corticoids (C) are used as measures of adrenal cortical function. However, they are not readily interpretable. Under different conditions, urinary 17-KS and FC can vary in the same sense or independently (Venning, 1950). Among factors contributing to this variability of relationship, the nature of the steroids undergoing metabolism is perhaps the most important. Thus, in human beings (Venning, 1950; Polley and Mason, 1950) and in rats (del Greco, Masson and Corcoran, 1952), only C-17-hydroxylated corticosteroids act as 17-KS precursors; the extent to which injected corticosteroids appear in urine as FC varies widely (Fajans, Louis and Conn, 1951 a). Among other variables are the state of esterification, the route of administration and the level of hepatic function (Fajans, Louis and Conn 1951 b; Engstrom et al., 1951; Bongiovanni and Eisenmenger, 1951).

TREATMENT of uninephrectomized rats with desoxycorticosterone acetate (DCA) and salt results in renal, splanchnic, myocardial and cerebral vascular lesions identical with those of experimental renal hypertension and similar in many respects to the lesions of hypertensive disease in human beings (Selye, 1942; Masson et al., 1949). The mechanism of formation of these lesions is unknown, except that arterial hypertension seems to be a contributory factor. That altered vascular permeability, with trapping in the vessel walls of a protein component of plasma might play a role in hyalinization and fibrinoid change in the arterioles is suggested in part by the microscopic appearance of some of these lesions. This possibility receives further support from the finding that desoxycorticosterone, in the presence of excess Na ion, increases permeability of vessels in preparations of isolated limbs (Tripod and Meier, 1952). The importance of increased permeability in this connection seems to have been confirmed by the...

SKELTON (1953) reported that methylandrostenediol (MAD) caused mild hypertension and vascular lesions in uninephrectomized rats given 1% NaCl as drinking fluid. In comparison with DCA, MAD caused more renal hypertrophy and greater degenerative changes in the adrenal cortex. The purpose of this study was to examine further the hypertensive effect of MAD and to define the nature of the adrenal lesions. Previous studied have demonstrated that other steroids which elicit hypertension, namely DCA, cortisone and hydrocortisone, sensitize rats to the pressor and vasculotoxic effects of renin (Masson, Corcoran and Page, 1951, 1952; Masson, del Greco, Corcoran and Page, 1953). Similar studies were made in animals pretreated with MAD. METHODS Female albino rats were uninephrectomized and divided in 3 groups of 10 animals each; group averages of body weights were respectively 196, 202, and 202 grams. Groups I and II were given MAD over 90 days, during which group III served as untreated controls.