Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency. I. The Role of Altered Glomerular Filtration Rate and Solute Excretion12

Abstract

The inability to excrete an oral or parenteral load of water in a normal manner is a characteristic of the adrenalectomized or hypophysectomized animal and of the patient with adrenal or pituitary insufficiency. The basic mechanisms responsible for impaired water tolerance in these diseases have not been adequately clarified, nor have the processes by which hydro-cortisone causes a normal water diuresis to occur. Welt postulated that the impaired water diuresis of these states is related primarily to alterations in the nonhormonal factors rather than to any disturbance in the secretion, metabolism, or action of antidiuretic hormone (ADH). If this theory is correct, it should be possible, while these subjects areunder the influence of a sustained water load, to improve considerably their response to water loading by techniques which increase glomerular filtration rate and alter the distribution of solute (Na) reabsorption between the proximal and distal tubule. This approach formed the basis of the present study. Aminophyllin was used to increase glomerular filtration acutely and alter the tubular reabsorption of solute. Its effect was compared in the same subject with the subsequent administration of hydrocortisone. The results indicate that the marked improvement in the excretion of water which followed the administration of hydrocortisone cannot be completely explained by improved renal hemodynamics or alteration of solute reabsorption. They support the view that Compound F-like steroids may, in the absence of ADH, specifically inhibit the back diffusion of water in the diluting segments of the nephron (loop of Henle and distal convoluted tubule) or prevent the reabsorption or back diffusion of water in the concentrating segment (? collecting tubule).