Composition of the Renal Medulla During Water Diuresis
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COMPOSITION OF THE RENAL MEDULLA DURING WATER DIURESIS Howard Levitin, … , Gilles Pigeon, Franklin H. Epstein J Clin Invest. 1962;41(5):1145-1151. https://doi.org/10.1172/JCI104567. Research Article Find the latest version: https://jci.me/104567/pdf Journal of Clinical Investigation Vol. 41, No. 5, 1962 COMPOSITION OF THE RENAL MEDULLA DURING WATER DIURESIS * By HOWARD LEVITIN,t ALVIN GOODMAN,* GILLES PIGEON § AND FRANKLIN H. EPSTEIN 11 (From the Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.) (Submitted for publication December 7, 1961; accepted January 15, 1962) During antidiuresis, sodium is concentrated in tubules in kidney sections from rats undergoing the papilla and medulla of mammalian kidneys as water diuresis was lower than that of cortex (3). a result of active sodium reabsorption from medul- Finally, direct micropuncture of loops of Henle lary tubules and countercurrent flow through the and vasa recta in hamsters with diabetes insipidus loops of Henle and the medullary capillaries. It yielded fluid with an osmolality higher than that is clear from chemical (1) and cryoscopic (2, 3) of vena cava plasma but lower than that observed analysis of sections of kidney, and from direct mi- in normal animals excreting a concentrated urine cropuncture (4-6), that under these circumstances (6). the osmolality of medullary interstitial fluid is ap- The present experiments were designed to clarify proximately that of collecting-duct urine and that the action of antidiuretic hormone on the sodium sodium concentration rises progressively along a content of the renal medulla. The chemical com- gradient from cortex to medulla. position of papilla, medulla, and cortex of dogs The precise role of antidiuretic hormone (ADH) was measured during hydropenia, during water in establishing and maintaining this gradient is not diuresis, and at varying intervals after the infusion entirely clear, partly because comparable studies of vasopressin. The results confirm previous evi- in the absence of vasopressin (i.e., during water dence that medullary fluid is hypertonic during diuresis) have been more difficult to accomplish. water diuresis, although not as concentrated as Ullrich, Jarausch and Drenckhahn demonstrated during hydropenia. They further indicate that, that the osmolality and sodium concentration of in addition to the fall in sodium concentration ex- papillary water approached that of peripheral pected as a result of an increase in water content., plasma in dogs during water diuresis (1, 7). water diuresis is associated with a decline in the That medullary interstitial fluid is actually hyper- absolute amount of sodium per unit of dry solids tonic to plasma in the absence of ADH was sug- in the renal medulla. The latter is restored by in- gested by the demonstration (8) that compression fusions of vasopressin or by dehydration. The of the renal artery of one kidney during water data suggest that, in addition to increasing the diuresis led to production of hypertonic urine by permeability of the collecting ducts to the back- that kidney. Recently, Bray reported that the diffusion of water, ADH enhances the sequestra- melting point of the contents of small medullary tion of sodium in the interstitial fluids of medulla and papilla. * Aided by grants from the American Heart Associa- tion, the National Heart Institute (H-834), the National METHODS Institute of Arthritis and Metabolic Diseases (2A-5015), Unanesthetized female mongrel dogs weighing 8 to 13 and the Lawrence Gelb Foundation. kg were trained to lie quietly with a urethral catheter in tEstablished Investigator of the American Heart place. Their standard dog ration was supplemented with Association. half a pound of horsemeat daily. All of the animals had t Postgraduate Fellow of the U. S. Public Health been previously tested and were not used if their urinary Service. osmolality after 24 hours of dehydration did not exceed § Traveling Fellow of the R. Samuel McLaughlin 1,400 mOsm! per kg of water. Foundation, 1960-1961; Research Fellow of the Connecti- Four groups of dogs were studied. The first group (6 cut Heart Association, 1961-1962. dogs) was studied during a water diuresis which had been 11 During the tenure of an Established Investigatorship induced 2 hours earlier by the intragastric administration of the American Heart Association. of water amounting to 5 per cent of their body weight. 1145 1146 LEVITIN, GOODMAN, PIGEON AND EPSTEIN tn 00 R 6 -H -H -HN o4 oo oo-H (O 0 0 0c3 00 00 00 oo. 0C 0 I'* r- N _ No C4N co K-4 4R N0s 0o) oo-H oH -_ -H -H -H-H --0- C4 NOO 0 0N 00 0 U\ N U) u 00 - U) ) u) C0) 0ON -H-H -H -H -H -H -H 0 0 O U)_ 00 0-4 U) 2 O "R -! 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U) O~ 'O Y o0o NU 0 00 f. co 04 00 00 N ,~ b4 N o N o . m 'N 00 ON ' ) U) ) U), Cd -H-H -H1+ 0co 4C o00 04 -H -H-H -H Cd N 00U N O N U)N '0u ._ -H-H 4i -H - ~-._NNN N00 u '0 U) Ok 0)0) '-m 0 .E S - U)00oo N 0 So S - N U)N 00 +0) oak NN t-0cu o U) t- U) * U) a Qg c q0 Z+V 1t NN No 1o oo ooe . o o '0-4i Ut N 0 -H>+4i -H-H- 'NCU a o- I- os t t ~~~~~~~~~o '00o 0)D c E- Q 4-- GO 4-) 0) 4.) 0) ~~~~~~~~~~~~~~~~~~~~4-)0))0)'0 0 *0 O- 0 0 0 0)0 co+ 0 0C0 0 0d co 0coco)2)Cd COMPOSITION OF THE RENAL MEDULLA DURING WATER DIURESIS 1 147 Group 2 (5 dogs) and group 3 (5 dogs) received a similar water load, followed 2 hours later, at the height of the en- suing water diuresis, by the intravenous infusion of vaso- pressin at the rate of 50 mU per kg per hour. Group 2 received the vasopressin infusion for 30 minutes, and group 3 received the vasopressin infusion for 2 hours. Group 4 (6 dogs) was studied during antidiuresis which resulted from 24 hours of food and water deprivation. In all dogs, timed urine collections were obtained prior to the conclusion of the experiment, at which time an intravenous injection of pentobarbital was given, and both kidneys were removed in 1 to 2 minutes. The pelvis of the kidney was opened and the longitudinal papillary ridge was exposed. A thin strip of this ridge WATER 30 MIN 2 HRS 24 HRS DIURESIS p ADH p ADH DEHYD. (papilla), 2 mm in thickness, was cut. A deeper longi- (6) (5) (5) (6) tudinal strip (medulla), 4 mm thick, was then dissected free. The capsule was stripped and pieces of cortex ob- FIG. 1. PAPILLARY CONTENT OF SODIUM AND POTAS- tained. Duplicate samples of papilla, medulla, and cortex SIUM PER 100 G DRY SOLIDS DURING WATER DIURESIS AND were examined. One sample was weighed by tare to con- AT VARYING STAGES OF ANTIDIURESIS. stant weight for water content. The other sample was ground in electrolyte-free, fine mesh carborundum and di- ture at the time the kidneys were clamped; in these cases luted with 7 ml of water (papilla and medulla) or 10 ml the specific activity of plasma sodium corresponded of water (cortex) and analyzed for sodium, potassium, closely to that of the sodium of renal cortex, suggesting ammonia, and urea, employing techniques previously pub- that in analyzing the data the specific activity of medul- lished (9). The average weight of the samples was as fol- lary or papillary sodium might conveniently be referred lows: papilla, 138 mg; medulla, 390 mg; cortex, 291 mg. to that of cortex. Four dogs were studied during water Urine samples were analyzed for the same solutes, as well diuresis and 5 after 24 to 48 hours of dehydration. as for osmolality, with a Fiske osmometer. In order to eliminate possible artifacts arising from losses of blood and interstitial fluid from the severed pedi- RESULTS cle of an unclamped kidney (10), two further groups of 5 dogs each were studied-one group during water diure- Composition of papilla, medulla, and cortex of sis and the other during hydropenia. In these experi- unclamped kidneys (Table I, Figure 1). The con- ments the renal pedicle was occluded with two large centration of solutes in tissue water [calculated as clamps. The renal artery, vein, and ureter were cut, and the sum of the concentrations of urea + 2(Na + the kidney with attached pedicle clamp was immediately K + increased frozen in acetone and dry ice. Cross sectional cuts near NH4)] progressively from cortex the middle of the frozen kidney were made with a power- to papilla in dehydrated dogs. This gradient was driven scroll saw. Duplicate samples of papilla, medulla, markedly reduced during water diuresis, a result and cortex, weighing an average of 169, 218, and 783 mg, of decreases in the concentration of sodium and respectively, were obtained.