Recent observations on the dog indicate that during recovery from chronic hypercapnia the chloride ion plays a critical role in permitting full restoration of plasma composition to normal (1). Plasma bicarbonate concentration remains significantly elevated, and plasma chloride concentration markedly depressed unless chloride is provided in the diet. It was tentatively proposed that when the quantity of chloride available for reabsorption is reduced, the transtubular potential difference generated by active transport of sodium is greater than normal and that this, in turn, is responsible for a higher than normal rate of diffusion of hydrogen ions into the glomerular filtrate and for the sustained elevation of plasma bicarbonate concentration.The present study was undertaken to determine whether chloride may play a significant role in the correction of the metabolic alkalosis associated with potassium deficiency. For this purpose, studies have been performed in dogs made potassium deficient, alkalotic, and hypochloremic by the administration of deoxycorticosterone acetate (DCA)' and sodium bicarbonate.Subsequently, three consecutive maneuvers were carried out while the animals were maintained on a diet low in potassium and chloride: 1) DCA was withdrawn, 2) potassium bicarbonate was substituted for sodium bicarbonate in the daily electrolyte supplement, and 3) chloride was administered in various forms.

Expansion of the plasma volume by infusions either of plasma or iso-oncotic albumin solution resulted almost uniformly in diuresis and natriuresis in anaesthetized dogs. Although the clearance of para-aminohippurate (RPF) usually increased, changes in clearance of creatinine (GFR) were neither large nor consistent in direction, indicating that the renal response depended on altered tubular reabsorption. The usual temporal dissociation between the peak values for water and sodium output during the response was interpreted as evidence of operation of two effector mechanisms. Reasons are given for believing that the renal response was not due to a direct action of the infusate, but rather to activation of a reflex mechanism by expansion of vascular volume. Bilateral cervical vagotomy did not prevent either the diuresis or the natriuresis, again implying that receptors additional to those in the cardiac atria must contribute to the sensory limb of the reflex. The average magnitude of diuretic and natriuretic responses after cervical vagotomy was, however, less than a quarter of that before the denervation, supporting the contention that the vagi do contribute to the renal response to expansion of the plasma volume when plasma is infused. The diuresis and the natriuresis still occurred during infusion in adrenalectomized animals, indicating that inhibition of aldosterone secretion is not the only effector mechanism leading to a natriuretic response to expansion of vascular volume.

Expansion of the plasma volume by infusions either of plasma or iso-oncotic albumin solution resulted almost uniformly in diuresis and natriuresis in anaesthetized dogs. Although the clearance of para-aminohippurate (RPF) usually increased, changes in clearance of creatinine (GFR) were neither large nor consistent in direction, indicating that the renal response depended on altered tubular reabsorption. The usual temporal dissociation between the peak values for water and sodium output during the response was interpreted as evidence of operation of two effector mechanisms. Reasons are given for believing that the renal response was not due to a direct action of the infusate, but rather to activation of a reflex mechanism by expansion of vascular volume. Bilateral cervical vagotomy did not prevent either the diuresis or the natriuresis, again implying that receptors additional to those in the cardiac atria must contribute to the sensory limb of the reflex. The average magnitude of diuretic and natriuretic responses after cervical vagotomy was, however, less than a quarter of that before the denervation, supporting the contention that the vagi do contribute to the renal response to expansion of the plasma volume when plasma is infused. The diuresis and the natriuresis still occurred during infusion in adrenalectomized animals, indicating that inhibition of aldosterone secretion is not the only effector mechanism leading to a natriuretic response to expansion of vascular volume.