Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat

Abstract

A B S T R A C T The exaggerated natriuresis of hypothyroid rats receiving a 5% saline infusion was studied to determine the mechanism and the site within the nephron responsible for this increase in sodium excretion. Sodium clearance (CNa) and fractional sodium excretion were both demonstrated to be greater in hypothyroid rats for any amount of sodium infused. The rate of increase in fractional sodium excretion in response to saline loading was 3.4 times greater in hypothyroid animals. At the conclusion of the diuresis some of the hypothyroid animals excreted greater than 45% of the filtered sodium load, while no control animal excreted more than 12% of the filtered sodium load.The mean clearance of insulin during the saline diuresis was 36.6% lower (P < 0.001) in the hypothyroid rats. D-Aldosterone given to hypothyroid animals 3 hr before the experiment did not alter the magnitude or rate of increase in fractional sodium excretion. Inulin space determinations in nephrectomized rats revealed that extracellular fluid volume was contracted by 17.1% in the hypothyroid rats (P < 0.01). Plasma sodium was not significantly different in hypothyroid and control animals.A limit on solute free water reabsorption (T'Huo) per osmolar clearance (Co..) was demonstrated in the hypothyroid rats when these animals excreted greater than 12% of the filtered osmotic load. The limit on TCH20 formation was associated with an acceleration in the rate of sodium excretion and a decline in the rate of potassium excretion. Early in the diuresis when Co.., CNa, and TCH20 were comparable in hypothyroid and control Received for publication 5 January 1970.rats, the filtered sodium load was 31% lower (P < 0.01) in the hypothyroid animals. These findings indicate that diminished thyroid hormone activity decreases renal sodium reabsorptive capacity. Indirect evidence suggests that the distal and possibly the proximal tubules are the sites of this diminished sodium reabsorption in hypothyroid animals. INTRODUCTIONHypothyroidism has profound effects on salt and water metabolism in the rat. These are manifested by an increase in water consumption and excretion (1), inability to elaborate a maximally concentrated urine (2), exaggerated natriuresis during a water or saline diuresis (3,4), and impaired ability to conserve sodium, resulting in a negative sodium balance and death when sodium intake is restricted (5). Fregly, Cade, Waters, Straw, and Taylor (4,6) have demonstrated a decreased secretory rate and tubular response to aldosterone in hypothyroid rats, and they have proposed that thyroid insufficiency influences sodium reabsorption through this indirect mechanism. Reville and Stephan (7), however, have recently presented evidence in adrenalectomized hypothyroid rats which suggested that the alteration of sodium metabolism observed in hypothyroid animals was independent of adrenal function. In the present study several of the factors which regulate sodium reabsorption were evaluated with the hope of determining what mechanism might be responsi...

Renal Sodium- and Potassium-Activated Adenosine Triphosphatase and Sodium Reabsorption in the Hypothyroid Rat

“…Renal function. Renal hemodynamics and sodium handling were measured during hydropenia in thyroidectomized and T3-treated rats, and results of each group compared with those of its own simultaneously studied controls (Table V) (1)(2)(3). Myxedematous patients have a decreased ability to excrete water loads and frequently manifest fluid retention and dilutional hyponatremia (3,4).…”

“…Thyroid-deficient animals and man exhibit numerous renal functional defects, including decreased renal plasma flow and glomerular filtration rate and impaired tubular reabsorption of sodium (1)(2)(3)(4). The mechanisms underlying these defects are incompletely understood.…”

“…Na-K-ATPase is involved in the active transport of sodium across epithelial membranes (7,8) and renal Na-K-ATPase specific activity parallels net sodium reabsorption by the kidney in a variety of physiological and experimental situations (9)(10)(11). Thyroid deficiency is known to reduce filtered and reabsorbed sodium (1,2) and could therefore affect enzymatic activity in this manner.…”

Mechanism of Impaired Water Excretion in the Hypothyroid Rat

“…Although no such apparent maximum for fractional CH2o was observed in the water diuresis experiments, it should be noted that distal delivery in these studies never exceeded 22% of GFR. Also of interest is the confirmation of a "sodium leak" in hypothyroid animals (3,4), in which fractional sodium clearance was higher than in controls during administration of massive sodium loads. However, the significance of this observation is not clear since in the same experiments net sodium excretion was not increased, and both net and fractional sodium excretion were lower in hypothyroid rats during water diuresis experiments in which the amount of sodium infused was smaller.…”

“…In the rat, hypothyroidism is associated with similar reductions in GFR and RPF, along with a defect in tubular sodium reabsorption and a limited renal concentrating ability (3,4). Data on urinary dilution in the hypothyroid rat are not available.…”