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

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 (C_Na/C_In) at any level of distal delivery of sodium compared to normal controls. Free water reabsorption (T^c_H2O) during hypertonic saline loading was quantitatively abnormal in the hypertensives at high levels of osmolar clearance (C_Osm), and also the curve of T^c_H2O vs. C_Osm leveled off above a C_Osm of 18 ml/min per 1.73 m² in the hypertensive group in contrast to the normal controls in whom T^c_H2O showed no evidence of achieving an upper limit. Sodium depletion exaggerated the abnormality in T^c_H2O in hypertensives, and resulted in a positive free water clearance (C_H2O) during hydropenia.

During hypotonic saline loading in water diuresis, changes in free water clearance per 100 ml of glomerular filtrate (C_H2O/C_In) were less at any given increment in urine flow per 100 ml of glomerular filtrate (V/C_In) in the hypertensives compared to normal controls (P < 0.001). This abnormality in C_H2O/C_In in the hypertensives in conjunction with the defect in T^c_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 T^c_H2O and C_H2O 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 hypertension, evidence was present also for enhanced rejection of sodium in the proximal tubule during saline loading in the hypertensives.

Additional studies utilizing acetazolamide which increases distal delivery of sodium without extracellular fluid volume expansion showed only minimal abnormalities in C_H2O in the hypertensive group, indicating that the defect in sodium transport in the loop of Henle in hypertensives is mainly an abnormal response to extracellular fluid expansion rather than an intrinsic defect in the loop to handle increased tubular loads of sodium. It is possible that the abnormality in sodium reabsorption in the loop of Henle is due to the transmission of the abnormally elevated blood pressure of the hypertensives to the medullary vasa recta during saline loading.

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