Free water reabsorption during solute diuresis in normal and potassium-depleted rats

A B S T R A C r The ability to excrete an oral water load and the renal diluting mechanism were studied in hypothyroid rats and in age-matched euthyroid controls. Hypothyroid animals excreted a significantly smaller fraction of a 50-ml/kg oral water load than controls, demonstrating the same limited ability to excrete free water as thyroid-deficient man. During hypotonic (0.45%) saline infusion, absolute sodium delivery to the diluting segment and free water clearance were markedly lower in hypothyroid rats. However, both fractional distal sodium delivery and fractional free water clearance were similar in hypothyroid and control animals, suggesting that the reduced absolute free water formation in hypothyroid rats was due to decreased net distal delivery. In support of this hypothesis was the observation that fractional distal sodium reabsorption was equal or higher in thyroid-deficient rats, which indicates that the sodium reabsorptive capacity of the diluting segment was preserved in these animals. The results cannot be attributed to incomplete suppression of antidiuretic hormone (ADH) since they were identical in diabetes insipidus rats, nor to different rates of non-ADH-dependent backflux of filtrate since tissue osmolality and solute concentrations in the cortex, medulla, and papilla were similar in hypothyroid and control rats of both Sprague-Dawley and Brattleboro strains.The functional integrity of the diluting segment in hypothyroid rats was further demonstrated in experiments in which distal delivery was increased by contralateral nephrectomy or by administration of carbonic anhydrase inhibitors which decrease proximal sodium reabsorption. In both studies, fractional free water clearance increased markedly reaching levels significantly greater than in euthyroid controls. INTRODUCTIONHypothyroid man exhibits numerous renal functional defects, including decrements in glomerular filtration rate (GFR) , effective renal plasma flow (RPF), maximal urine osmolality, and free water generation and reabsorption (1, 2). 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.The most important clinical consequence of the renal functional defects in hypothyroid man is water retention and dilutional hyponatremia, due to the limited ability of the kidney to generate free water. The mechanism underlying this defect remains undefined, being variously attributed to inappropriate secretion of or increased tubular sensitivity to vasopressin (5-8), relative deficiency of adrenocortical hormones (9), defective distal sodium reabsorption (1), and decreased delivery of filtrate to the distal diluting segment (1, 2).The present study was designed to evaluate the renal diluting process in hypothyroid rats and to examine in this species some of the pathogenetic mechanisms ad1Abbreviations used in this paper: ADH, antidiuretic (Charles Ri...

Section: Discussionmentioning

confidence: 56%

Mechanism of Impaired Water Excretion in the Hypothyroid Rat

Emmanouel¹,

Lindheimer²,

Katz³

1974

“…10). The large and variable (according to the osmotic gradient) amount of sodium reabsorbed out of the ascending limb suggests that the active transport was not Tm limited, but had the Na concentration gradient as a limiting factor; this has been already suggested by several authors (22,(31)(32)(33).…”

Section: Mechanism Of Concentrationmentioning

confidence: 70%

Micropuncture study of water, electrolytes, and urea movements along the loops of henle in psammomys

Rouffignac¹,

Morel²

1969

149

A B S T R A C T The mechanism by which the osmotic pressure increases in tubular fluid along the descending limb of the loop of Henle was examined in Psammomys undergoing salt diuresis. In two series of experiments, micropuncture samples were collected either from proximal and distal convolutions at the surface of the cortex, or from loops of Henle and collecting ducts at the surface of the extrarenal part of the papilla. Inulin-'H, urea-14C, Na+, and K+ concentrations, as well as osmotic pressure, were determined in all micropuncture samples.Net movements of water along the descending and ascending limbs of the loop could not be deduced by comparing inulin data obtained from convoluted tubules and from loops of Henle, since there appeared to be a large difference in the filtration rate of the superficial glomeruli (9 nl/min) and the deep ones (21.4 nl/min) under the conditions of these experiments.The results indicate that no large net movement of water occurred along the loop since a) only 23% of the filtrate was reabsorbed along the loop of Henle (including pars recta) of superficial nephrons despite the fact that all these loops reached markedly hypertonic regions; b) there was no positive correlation between (F/P) in early distal samples and the simultaneous osmotic pressure of the urine; c) when (F/P)In and (F/P)osm in loop samples were correlated, the increase in inulin concentration accounted only for 15% of the increase in osmotic pressure. Therefore, 85% of the concentrating process taking place along the descending limb must have resulted from net addition of solutes; this was directly supported by Na+ and K+ measurements in the loop samples, which showed that, at the tip of A partial report of this work was presented at the XXIV

“…Potassium depletion by itself may cause a defect in sodium reabsorption in the loop of Henle (38). Two of our patients were potassium depleted at the time of study due to hyperaldosteronism.…”

Section: Studies During Water Diuresismentioning

confidence: 80%

Mechanism of exaggerated natriuresis in hypertensive man: impaired sodium transport in the loop of henle

Buckalew¹,

Puschett²,

Kintzel³

et al. 1969

A B S T R A C T To evaluate the effects of saline loading on distal sodium reabsorption in hypertensive man, studies were performed during both water deprivation and water diuresis in eight hypertensive subjects, and the results were compared to data obtained from similar studies in normal subjects. All hypertensive patients exhibited an enhanced excretion of filtered sodium (Ca/CIn) at any level of distal delivery of sodium compared to normal controls. Free water reabsorption (TCH2o) during hypertonic saline loading was quantitatively abnormal in the hypertensives at high levels of osmolar clearance (Co.m), and also the curve of TCHIo vs. Co.m leveled off above a Co.m of 18 ml/min per 1.73 m' in the hypertensive group in contrast to the normal controls in whom TCH,0o showed no evidence of achieving an upper limit. Sodium depletion exaggerated the abnormality in T'Ho in hypertensives, and resulted in a positive free water clearance (CH2o) during hydropenia.During hypotonic saline loading in water diuresis, changes in free water clearance per 100 ml of glomerular filtrate (CIo0/CI.) were less at any given increment in urine flow per 100 ml of glomerular filtrate (V/CG.) in the hypertensives compared to normal controls (P < 0.001). This abnormality in CH2o/CI. in the hypertensives in conjunction with the defect in T'H2o observed during hydropenia indicates that sodium reabsorption in the loop of Henle was abnormal at any given rate of distal delivery of sodium in hypertension. Furthermore, these abnormalities in TCH2o and CH20 coincided temporally with the development of the exaggerated natriuresis. Although the distal defect in sodium transport, in large part, accounted for the augmented natriuresis in hyperThis work was presented in part at the 1st Annual Meeting of the