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Daily doses (5 mg) of 1-dehydrohydrocortisone reduces plasma Na and Cl of nonfasted adrenalectomized dogs to levels characteristic of severe insufficiency. The animals remain active and vigorous despite the distorted plasma electrolyte pattern. Blood pressure and plasma volume remain at or near control values. The glucocorticoid maintains a normal internal distribution of fluid and certain electrolytes between intra- and extracellular compartments. Aldosterone even in large doses apparently lacks those properties necessary to enable the fasted adrenalectomized dog exhibiting symptoms to shift fluids from one compartment to another hence is incapable of reviving animals from insufficiency and restoring activity and vigor. The data suggest that the primary action of aldosterone is on the kidney and through renal control of Na excretion serves to regulate the fluid and Na content of the extracellular compartment.

The effects of large amounts of various adrenal steroids on the electrocardiogram of the adrenalectomized dog are described. The changes which occurred most frequently fell into 2 major groups: (1) those following excess of mineralo-corticoids, e.g., desoxycorticosterone and aldosterone, and (2) those appearing after gluco-corticoid administration. A characteristic type of diphasic T wave frequently followed treatment with hydrocortisone and its analogs, and its correction was hastened by substituting mineralo-corticoid therapy. The 3 analogs of hydrocortisone (dexamethasone, prednisolone and triam$$$inolone) induce similar electrocardiographic patterns and after prolonged administration alter the P-Q interval in varying degrees, but more frequently produce a diphasic T. Dexamethasone preserves the normal pattern longer than the other steroids tested.

75glands known to influence pigmentation did not significantly alter the occurrence of hyperpigmentation in irradiated mice. Hawever, that this process is not entirely refractory to hormones is evidenced by inhibition of melanin formation in irradiated mice treated with large doses of exogenous cortisone or of diethylstilbestrol.Summary. C57BL and LAFl mice became hyperpigmented in the extremities when exposed daily to gamma radiation. This process was not significantly altered by adrenalectomy, castration or daily treatment with ACTH. Hypophysectomized black rats, Xirradiated weekly, developed hyperpigmentation at the same rate as controls. Although it would appear that induction of hyperpigmentation by radiations is largely free of endocrine control, daily treatment of gamma irradiated mice with large doses of cortisone will suppress pigment formation.Glucocorticoids readily restore to normal the markedly disturbed fluid and electrolyte equilibria of adrenalectomized dogs exhibitings severe insufficiency. This is accomplished in animals deprived of food and water, by hormonal mobilization and shift of fluid and electrolytes from cells and certain tissues to the dehydrated extracellular (and intravascular) compartment. Experiments reprted here indicated that aldasterone and DOC are * Acknowledgement is made for financial and other valuable aid: Upjohn Co., Ciba Pharmaceutical Products Co., Merck, Sharp & Dohme, N. J. Heart Assn., National Science Fn., and Nat. Inst. of Arthritis and Metabolic Diseases, USPHS. Aldosterone was supplied by Ciba Ltd.'o€ Basle. t New Jersey Heart Assn. incapable of relieving severe symptoms oi adrenal insufficiency or of inducing internal redistrilbution of fluid and electrolytes in the fasted dog. The data suggest tentative assignment of certain functional roles for mint eralo-and glucocorticoids in regulatory control of salt and water balance. The materials and methods used in studies on adrenalectomized dogs have been adequately described W). Results. Effect of 2-methyl-9a-fluorohydrocortisone, Aldosterone and Desoxycerticosterone on plasma and urine electrolytes and Niismd volume of fasted adrenalectomized om insufficiency. A . 2met hyl-9a-fluoroh ydrocortisone (2-met hyl FF free alcohol). Five dogs were tested and toby guest on July 24, 2015 ebm.sagepub.com Downloaded from

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