Importance of Residual Water Permeability on the Excretion of Water during Water Diuresis in Rats

Abstract

When the concentration of sodium (Na(+)) in arterial plasma (P(Na)) declines sufficiently to inhibit the release of vasopressin, water will be excreted promptly when the vast majority of aquaporin 2 water channels (AQP2) have been removed from luminal membranes of late distal nephron segments. In this setting, the volume of filtrate delivered distally sets the upper limit on the magnitude of the water diuresis. Since there is an unknown volume of water reabsorbed in the late distal nephron, our objective was to provide a quantitative assessment of this parameter. Accordingly, rats were given a large oral water load, while minimizing non-osmotic stimuli for the release of vasopressin. The composition of plasma and urine were measured. The renal papilla was excised during the water diuresis to assess the osmotic driving force for water reabsorption in the inner medullary collecting duct. During water diuresis, the concentration of creatinine in the urine was 13-fold higher than in plasma, which implies that ~8% of filtered water was excreted. The papillary interstitial osmolality was 600 mOsm/L > the urine osmolality. Since 17% of filtered water is delivered to the earliest distal convoluted tubule micropuncture site, we conclude that half of the water delivered to the late distal nephron is reabsorbed downstream during water diuresis. The enormous osmotic driving force for the reabsorption of water in the inner medullary collecting duct may play a role in this reabsorption of water. Possible clinical implications are illustrated in the discussion of a case example.

Keywords: basal water permeability; desalination; polyuria; vasopressin.

Fig. 1

Effect of a Large Water Diuresis on the (U/P)_Creatinine in Rats Given a Large Oral Water Load. The (U/P)_Creatinine is depicted on the y-axis and the time of collection of the urine is shown on the x-axis. The results are from 6 separate rats, as indicated by the different symbols. Once the maximum water diuresis began, the (U/P)_Creatinine was virtually constant. The (U/P)_Creatinine was somewhat more than 2-fold larger than 6 (the dashed horizontal line), which suggests that close to half of the distal delivery of filtrate was reabsorbed downstream for the early distal convoluted tubule, presumably from the inner medullary collecting duct via residual water permeability.

Fig. 2

Contribution of Residual Water Permeability to the Excretion of Water during a Water Diuresis When the Urine Flow Rate is very High and When It Has Decreased. The structures to the left of the dashed vertical line represent a very large water diuresis and the structures to the right of the dashed vertical line represent a modest water diuresis owing to a lower distal delivery of filtrate and a larger reabsorption of water in the inner medullary collecting duct. The upper cylinder of each figure represents the inner medullary collecting duct with bolder outlines to indicate its limited capacity for it to dilate. The inverse triangular structure below it represents the renal pelvis. The arrow below represents fluid that bypasses the retrograde flow and enters the bladder. The numeric values are for illustrative purposes (see text for details).

Fig. 3

Desalination of Luminal Fluid in the Medullary Thick Ascending Limb of the Loop of Henle and in the Cortical Distal Nephron. When more Na⁺ and Cl^- are reabsorbed without water, fewer electrolytes will be excreted in a water diuresis. The stimulus begins with a high flow rate in the inner medullary collecting duct (MCD), which leads to more water reabsorption via residual water permeability (shown as a shaded oval near the 'start here' message). As a result, there is a signal (lower concentration of ionized calcium in the outer medullary interstitial compartment), which may increase the reabsorption of Na⁺ and Cl^- in the medullary thick ascending limb of the loop of Henle (mTAL) to begin the desalination process. In the late cortical distal nephron (abbreviated as CCD), flow activation of the epithelial Na⁺ channels (ENaC) accelerates Na⁺ reabsorption. cTAL, cortical thick ascending limb; DCT, distal convoluted tubule.