James G. Hilton

Adrenocorticotropic Action of Antidiuretic Hormone

By means of direct arterial perfusion of the adrenal glands of the hypophysectomized dog, it has been shown that synthetic lysine, arginine and acetyl arginine vasopressins stimulate the adrenal cortex directly to secrete hydrocortisone. Pressor activity and cortisol-stimulating activity were demonstrated to be independent of each other. Similar polypeptides, such as oxytocin, insulin, glucagon, and pressor amines, such as epinephrine and norepinephrine, did not show any cortisol-stimulating activity. ACTH was found consistently to increase the rate of secretion of aldosterone when perfused through the glands of hypophysectomized animals. The probable role of arginine vasopressin as an important factor in the stress reaction is considered along with its postulated ability to activate adrenal phosphorylase.

A new guanidine diuretic, amipramizide: Reduction of the kaliuretic effect of ethacrynic acid in man

Metabolic balance studies were carried out in four patients with refractory edema with the use of the guanidine diuretic, amipramizide (MK 870), and ethacrynic acid. MK 870 caused limited natriuresis and little or no weight loss. In all patients ethacrynic acid induced natriuresis and weight loss. With ethacrynic acid and MK 870, potassium balance in the cardiac patient remained at control values. One cirrhotic patient was maintained in normal potassium balance with normal serum electrolytes. In the other cirrhotic patients there was negative potassium balance but it was of lesser magnitude with milder degrees of hypokalemic alkalosis. In all patients the natriuresis and weight loss were greater than after ethacrynic acid alone.

Direct stimulation of adrenocortical secretion by synthetic vasopressin in dogs.

Summary By means of direct arterial perfusion of the adrenal glands in the dog it has been shown that synthetic vasopressin stimulates secretion of hydrocortisone. This effect is not mediated via the adenohypophysis or any other organ, but is rather the result of direct stimulation of the adrenal cortex by vasopressin itself.

Renal and Adrenal Relationships in Refractory Edema

The relationships between the excretion of sodium and water and adrenal activity in patients with refractory edema have been investigated. Experiments have been performed over a prolonged period with varying doses and combinations of spironolactone, prednisone, hydrochlorothiazide, Su4885, and ACTH. In four patients with Laennecs cirrhosis with ascites the effects of prednisone on the excretion of water and solute were studied during maximum water diuresis. The results indicate that diuretic agents may increase the excretion of sodium without water within certain undefined limits. This effect probably resulted from the delivery to the concentrating segment of an amount of sodium inadequate to dissipate the gradients favoring water reabsorption. Prednisone appeared to have a dual effect: one on the excretion of water, the other on the excretion of sodium. The effects on sodium and water did not appear to be related. The effects of prednisone on the excretion of water support the concept that the glucocorticoids exert an effect on water in the renal tubules rather than on the posterior pituitary. Prednisone enhanced sodium excretion only when given together with another diuretic agent. It is suggested that the failure of prednisone alone to increase sodium excretion resulted from a blockade of ACTH secretion and, thereby, the adrenal synthetic pathway of aldosterone, whereas the renal aldosterone-stimulating pathway continued to function. The potentiating effect of prednisone on the excretion of sodium becomes apparent only when aldosterone activity is overcome in the renal tubules by the natriuretic effects of various diuretics. It is considered possible that renal aldosterone-stimulating hormone acts only under more intense stimuli to edema formation.

Effects of clomiphene on adrenal cortical steroidogenesis in dogs

Abstract The mechanism of action of clomiphene, the ovulation inducing agent, remains uncertain. Most of the evidence has been interpreted to reflect a weak estrogen-like action and an estrogen inhibitory influence at higher concentrations. Direct adrenal cortical effects have also been postulated. The present study was undertaken to test the latter hypothesis by perfusing the isolated adrenal of the hypophysectomized dog with clomiphene. No alteration in either the resting 17-OH corticosteroid or 17-ketosteroid secretion rates was observed after 3 doses of clomiphene. It appears unlikely that clomiphene acts directly on the adrenal cortex.