Abstract
To study the renal medullary transport and accumulation of urea in dogs independent of water transport, we obliterated the medullary electrolyte gradient by a sustained ethacrynic acid diuresis. Infusions of urea were also given at various rates to vary urinary urea concentration. In the steady state, the kidneys were removed, and slices were analyzed for water, urea, and electrolytes. In every experiment in 15 dogs over a range of urinary urea concentration from 19 to 230 mmoles per L and urine flow from 0.5 to 9.7 ml per minute per kidney, an intrarenal urea gradient persisted, and urinary urea concentration was always lower than papillary water urea concentration. The magnitude of this uphill urinary-papillary gradient (mean ± SE = - 21 ± 2.9 mmoles per L) was not affected by hemorrhagic hypotension or a nonprotein diet.
In 12 additional experiments begun similarly, inhibitors were infused into one renal artery. Both iodoacetate, an inhibitor of anaerobic glycolysis, and acetamide, an analogue of urea, markedly and significantly reduced both the intrarenal urea gradient and the uphill urinary-papillary gradient. In contrast, cyanide, an inhibitor of oxidative metabolism, had no observable effect on the urea gradients. The data are best explained by postulating an active transport system for urea in the medullary collecting duct deriving its energy from anaerobic glycolysis.
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Selected References
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- AUKLAND K. Renal tubular permeability to urea with special reference to accumulation of urea in the renal medulla. Scand J Clin Lab Invest. 1961;13:646–660. doi: 10.3109/00365516109137339. [DOI] [PubMed] [Google Scholar]
- BERLINER R. W., LEVINSKY N. G., DAVIDSON D. G., EDEN M. Dilution and concentration of the urine and the action of antidiuretic hormone. Am J Med. 1958 May;24(5):730–744. doi: 10.1016/0002-9343(58)90377-2. [DOI] [PubMed] [Google Scholar]
- BRAY G. A., PRESTON A. S. Effect of urea on urine concentration in the rat. J Clin Invest. 1961 Nov;40:1952–1960. doi: 10.1172/JCI104420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BRODSKY W. A., CARLISKY N. J., GONZALEZ C. F., SHAMOO Y. E. METABOLIC PATHWAYS FOR UREA PRODUCTION BY THE AMPHIBIAN KIDNEY. Am J Physiol. 1965 Mar;208:546–554. doi: 10.1152/ajplegacy.1965.208.3.546. [DOI] [PubMed] [Google Scholar]
- CRAWFORD J. D., DOYLE A. P., PROBST J. H. Service of urea in renal water conservation. Am J Physiol. 1959 Mar;196(3):545–548. doi: 10.1152/ajplegacy.1959.196.3.545. [DOI] [PubMed] [Google Scholar]
- Clapp J. R. Renal tubular reabsorption of urea in normal and protein-depleted rats. Am J Physiol. 1966 Jun;210(6):1304–1308. doi: 10.1152/ajplegacy.1966.210.6.1304. [DOI] [PubMed] [Google Scholar]
- EARLEY L. E., FRIEDLER R. M. RENAL TUBULAR EFFECTS OF ETHACRYNIC ACID. J Clin Invest. 1964 Jul;43:1495–1506. doi: 10.1172/JCI105026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FUJIMOTO M., NASH F. D., KESSLER R. H. EFFECTS OF CYANIDE, QO, AND DINITROPHENOL ON RENAL SODIUM REABSORPTION AND OXYGEN CONSUMPTION. Am J Physiol. 1964 Jun;206:1327–1332. doi: 10.1152/ajplegacy.1964.206.6.1327. [DOI] [PubMed] [Google Scholar]
- GARDNER K. D., Jr, MAFFLY R. H. AN IN VITRO DEMONSTRATION IN INCREASED COLLECTING TUBULAR PERMEABILITY TO UREA IN THE PRESENCE OF VASOPRESSIN. J Clin Invest. 1964 Oct;43:1968–1975. doi: 10.1172/JCI105070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOLDBERG M., MCCURDY D. K., FOLTZ E. L., BLUEMLE L. W., Jr EFFECTS OF ETHACRYNIC ACID (A NEW SALURETIC AGENT) ON RENAL DILUTING AND CONCENTRATING MECHANISMS: EVIDENCE FOR SITE OF ACTION IN THE LOOP OF HENLE. J Clin Invest. 1964 Feb;43:201–216. doi: 10.1172/JCI104905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grantham J. J., Burg M. B. Effect of vasopressin and cyclic AMP on permeability of isolated collecting tubules. Am J Physiol. 1966 Jul;211(1):255–259. doi: 10.1152/ajplegacy.1966.211.1.255. [DOI] [PubMed] [Google Scholar]
- HERMS W., MALVIN R. L. Effect of metabolic inhibitors on urine osmolality and electrolyte excretion. Am J Physiol. 1963 Jun;204:1065–1070. doi: 10.1152/ajplegacy.1963.204.6.1065. [DOI] [PubMed] [Google Scholar]
- JAENIKE J. R. The influence of vasopressin on the permeability of the mammalian collecting duct to urea. J Clin Invest. 1961 Jan;40:144–151. doi: 10.1172/JCI104228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JARAUSCH K. H., ULLRICH K. J. Untersuchungen zum Problem der Harnkonzentrierung und Harnverdünnung; Uber die Verteilung von Elektrolyten (Na, K, Ca, Mg, Cl, anorganischem Phosphat), Harnstoff, Aminosäuren und exogenem Kreatinin in Rinde und Mark der Hundeniere bei verschiedenen Diuresezuständen. Pflugers Arch. 1956;262(6):537–550. doi: 10.1007/BF00362116. [DOI] [PubMed] [Google Scholar]
- KEAN E. L., ADAMS P. H., WINTERS R. W., DAVIES R. E. Energy metabolism of the renal medulla. Biochim Biophys Acta. 1961 Dec 23;54:474–478. doi: 10.1016/0006-3002(61)90087-7. [DOI] [PubMed] [Google Scholar]
- KIIL F., AUKLAND K. The role of urea in the renal concentration mechanism. Scand J Clin Lab Invest. 1960;12:290–299. doi: 10.3109/00365516009062439. [DOI] [PubMed] [Google Scholar]
- KLUMPER J. D., ULLRICH K. J., HILGER H. H. Das Verhalten des Harnstoffs in den Sammelrohren der Säugetierniere. Pflugers Arch. 1958;267(3):238–243. doi: 10.1007/BF00362427. [DOI] [PubMed] [Google Scholar]
- LASSITER W. E., GOTTSCHALK C. W., MYLLE M. Micropuncture study of net transtubular movement of water and urea in nondiuretic mammalian kidney. Am J Physiol. 1961 Jun;200:1139–1147. doi: 10.1152/ajplegacy.1961.200.6.1139. [DOI] [PubMed] [Google Scholar]
- LEVINSKY N. G., BERLINER R. W. The role of urea in the urine concentrating mechanism. J Clin Invest. 1959 May;38(5):741–748. doi: 10.1172/JCI103854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEVINSKY N. G., DAVIDSON D. G., BERLINER R. W. Effects of reduced glomerular filtration on urine concentration in the presence of antidiuretic hormone. J Clin Invest. 1959 May;38(5):730–740. doi: 10.1172/JCI103853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lassiter W. E., Mylle M., Gottschalk C. W. Micropuncture study of urea transport in rat renal medulla. Am J Physiol. 1966 May;210(5):965–970. doi: 10.1152/ajplegacy.1966.210.5.965. [DOI] [PubMed] [Google Scholar]
- MAFFLY R. H., HAYS R. M., LAMDIN E., LEAF A. The effect of neurohypophyseal hormones on the permeability of the toad bladder to urea. J Clin Invest. 1960 Apr;39:630–641. doi: 10.1172/JCI104078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- OWEN E. E., ROBINSON R. R. UREA PRODUCTION AND EXCRETION BY THE CHICKEN KIDNEY. Am J Physiol. 1964 Jun;206:1321–1326. doi: 10.1152/ajplegacy.1964.206.6.1321. [DOI] [PubMed] [Google Scholar]
- RABINOWITZ L., KELLOGG R. H. Enhancement of renal concentrating ability in the dog by urea and related compounds. Am J Physiol. 1963 Jul;205:112–116. doi: 10.1152/ajplegacy.1963.205.1.112. [DOI] [PubMed] [Google Scholar]
- SCHMIDT-NIELSEN B., O'DELL R. Effect of diet on distribution of urea and electrolytes in kidneys of sheep. Am J Physiol. 1959 Oct;197:856–860. doi: 10.1152/ajplegacy.1959.197.4.856. [DOI] [PubMed] [Google Scholar]
- SCHMIDT-NIELSEN B., RABINOWITZ L. METHYLUREA AND ACETAMIDE: ACTIVE REABSORPTION BY ELASMOBRANCH RENAL TUBULES. Science. 1964 Dec 18;146(3651):1587–1588. doi: 10.1126/science.146.3651.1587. [DOI] [PubMed] [Google Scholar]
- Schirmer H. K. The effect of intermittent and prolonged renal artery occlusion upon respiration and anaerobic glycolysis of dog kidney. J Urol. 1965 Nov;94(5):511–513. doi: 10.1016/S0022-5347(17)63660-7. [DOI] [PubMed] [Google Scholar]
- TRUNIGER B., SCHMIDT-NIELSEN B. INTRARENAL DISTRIBUTION OF UREA AND RELATED COMPOUNDS: EFFECTS OF NITROGEN INTAKE. Am J Physiol. 1964 Nov;207:971–978. doi: 10.1152/ajplegacy.1964.207.5.971. [DOI] [PubMed] [Google Scholar]
