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Biologischer Nachweis eines humoralen natriuretischen Prinzips im Urin gesunder Menschen

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Zusammenfassung

In früheren eigenen Untersuchungen konnte erwiesen werden, daß eine wiederholte mäßige orale Flüssigkeitsbelastung an gesunden Versuchspersonen durch Hemmung der tubulären Reabsorption zu einer Steigerung der renalen Natriumausscheidung führt.

Zum Nachweis eines humoralen Faktors, der für diese Natriurese verantwortlich sein könnte, wurden durch Dialyse und Ultrafiltration gewonnene Fraktionen aus dem Urin derart vorbehandelter Versuchspersonen an natriumverarmten Ratten nach kombinierter oraler und intravenöser Belastung mit isotoner Kochsalzlösung auf ihre natriuretische Wirksamkeit untersucht. Der Urin wurde nach Einbringung der Tiere in Einzelstoffwechselkäfige 5 Std lang gesammelt, Urinvolumen, Natrium-, Chlorid- und Kaliumausscheidung wurden auf 100 g Körpergewicht/5 Std errechnet. Während die Kontrolltiere nahezu 50% des angebotenen Natrium retinieren (Na/K-Quotient 0,88), führt eine einzige i.v. Injektion von 25 µg MRL zum Anstieg der Natriumausscheidung. Die Kaliumausscheidung bleibt unverändert, der Na/K-Quotient erreicht einen Normwert von 2,0. Die negative freie Wasserclearance ist unter der Einwirkung von 25 µg des Urinextraktes signifikant reduziert. Daraus läßt sich auf eine Abnahme des anisosmotischen Natriumtransportes unter der Einwirkung des natriuretischen Prinzips schließen.

Die Ergebnisse weisen auf einen Rückgang der tubulären Natrium-Reabsorption hin und liefern den Beweis für die Existenz eines humoralen natriuretischen Faktors im Urin gesunder Versuchspersonen nach mäßiger oraler Flüssigkeitsbelastung.

Summary

Recently we demonstrated an increased renal sodium excretion without changes in tubular sodium load after moderate continuous oral hydration in normal man. To evaluate the possible existence of a humoral factor responsible for the natriuresis, urine preparations of hydrated normal persons were tested for natriuretic activity in a specially developed bioassay in rats. Urines were dialyzed and ultrafiltered. The lyophilized membrane residue was dissolved in isotonic saline. Sodium depleted rats received sodium in an amount of 750 µEq by gavage and 150 µEq intravenously. The animals were kept under standardized conditions in single metabolic cages. Urine was collected for five hours. Urine volume, osmolal clearance, sodium, chloride and potassium excretion were calculated for 100 g body weight/5 hours. Of the given sodium load, control animals retained almost 50% (mean: 222 of 470 µEq/100 g/5 hrs). Inspite of the sodium loading the urinary sodium: potassium ratio was reduced to 0.88. Intravenous injection of the urine preparations resulted in a dose-dependent decrease in the sodium retention with an increase in the sodium: potassium ratio to 2.0 at doses of 25 µg, potassium excretion being unaltered. The free water reabsorption was significantly reduced. The effect of this dose exceeded that of 50 µg of hydrochlorothiazide. The results point to a decrease of tubular sodium reabsorption and give evidence for the existence of a humoral natriuretic factor present in normal man after moderate oral hydration.

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Literatur

  • Adlersberg, D.: Zur Rolle der Leber im Wasserhaushalt. Klin. Wschr.13, 393 (1934).

    Google Scholar 

  • August, J. T., D. H. Nelson, andG. W. Thorn: Response of normal subjects to large amounts of aldosterone. J. clin. Invest.37, 1549 (1958).

    Google Scholar 

  • Bartter, F. C., G. W. Liddle, L. E. Duncan, J. K. Barber, andC. Delea: The regulation of aldosterone secretion in man: the role of fluid volume. J. clin. Invest.35, 1306 (1956).

    Google Scholar 

  • Beck, J. C., I. Dyrenfurth, C. Giroud, andE. H. Venning: Observations on the regulatory mechanisms of aldosterone secretion in man. Arch. intern. Med.96, 463 (1955).

    Google Scholar 

  • Blythe, W. B., andL. G. Welt: Dissociation between filtered load of sodium and its rate of excretion in the urine. J. clin. Invest.42, 1491 (1963).

    Google Scholar 

  • Bresler, E. H.: Reabsorptive response of renal tubules to elevated sodium and chloride concentrations in plasma. Amer. J. Physiol.199, 517 (1960).

    Google Scholar 

  • Cirksena, W. J., J. H. Dirks, andR. W. Berliner: Effect of thoracic cava obstruction on response of proximal tubule sodium reabsorption to saline infusion. J. clin. Invest.45, 179 (1966).

    Google Scholar 

  • Crawford, B., andH. Ludeman: The renal response of intravenous injection of sodium chloride solutions in man. J. clin. Invest.30, 1456 (1951).

    Google Scholar 

  • Deming, Q. B., andJ. A. Luetscher jr.: Bioassay of desoxycorticosterone-like material in urine. Proc. Soc. exp. Biol. (N.Y.)73, 171 (1950).

    Google Scholar 

  • Dirks, J. H., W. J. Cirksena, andR. W. Berliner: The effect of saline infusion on sodium reabsorption by the proximal tubule of the dog. J. clin. Invest.44, 1160 (1965).

    Google Scholar 

  • Frey, E.: Der Mechanismus der Salz- und Wasserdiurese. Pflüg. Arch. ges. Physiol.112, 71 (1906).

    Google Scholar 

  • Giebisch, G.: Electrical potential measurements on single nephrons of Necturus. J. cell. comp. Physiol.51, 221 (1958).

    Google Scholar 

  • Giebisch, G., R. M. Klose, G. Malnic, W. J. Sullivan, andE. E. Windhager: Sodium movement across single perfused proximal tubules of rat kidneys. J. gen. Physiol.47, 1175 (1964).

    Google Scholar 

  • Ginsberg, W.: Diureseversuche. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.69, 381 (1912).

    Google Scholar 

  • Haberich, F. J., O. Aziz, u.P. E. Nowacki: Über das unterschiedliche Verhalten der Diurese bei intraportalen und intracavalen Infusionen von Wasser und 0,9% NaCl-Lösung an der wachen Ratte. Pflüg. Arch. ges. Physiol.279, R 30 (1964);

  • Über einen osmoreceptorisch tätigen Mechanismus in der Leber. Pflüg. Arch. ges. Physiol.285, 73 (1965).

    Google Scholar 

  • Hashimoto, M.: Zur Frage der aus dem Verdauungstrakt darstellbaren diuretisch wirksamen Substanz. Naunyn Schmiedebergs Arch. exp. Path. Pharmakol.76, 367 (1914).

    Google Scholar 

  • Johnston, C. I., andJ. O. Davis: Evidence from cross circulation studies for a humoral mechanism in the natriuresis of saline loading. Proc. Soc. exp. Biol. (N.Y.)121, 1058 (1966).

    Google Scholar 

  • Jones, N. F., M. A. Barraclough, andI. H. Mills: The mechanism of increased sodium excretion during water loading with 2,5% dextrose and vasopressin. Clin. Sci.25, 449 (1963).

    Google Scholar 

  • Kamm, D. E., andN. G. Levinsky: Effect of plasma sodium elevation on renal sodium reabsorption. Amer. J. Physiol.206, 1131 (1964);

    Google Scholar 

  • Inhibition of renal tubular sodium reabsorption by hypernatriemia. J. clin. Invest.44, 1144 (1965).

    Google Scholar 

  • Krecke, H.-J. u.F. Krück: Die Natriurese bei oraler Hydratation. Verh. dtsch. Ges. inn. Med.70, 977 (1964).

    Google Scholar 

  • Krück, F., andH.-J. Krecke: The renal sodium excretion during oral hydration in man. Nephron2, 321 (1965).

    Google Scholar 

  • Leaf, A., F. C. Bartter, R. F. Santos, andO. Wrong: Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J. clin. Invest.32, 868 (1953).

    Google Scholar 

  • Levinsky, N. G., andR. C. Lalone: The mechanism of sodium diuresis following saline infusion in the dog. J. clin. Invest.42, 1261 (1963);

    Google Scholar 

  • Sodium excretion during acute saline loading in dogs with vena caval constriction. J. clin. Invest.44, 565 (1965).

    Google Scholar 

  • Lichardus, B., andJ. W. Pearce: Hemodynamic and humoral factors in natriuresis following blood volume expansion. Fed. Proc.24, 404 (1965);

    Google Scholar 

  • Evidence for a humoral natriuretic factor released by blood volume expansion. Nature (Lond.)209, 407 (1966).

    Google Scholar 

  • Little, J. M., E. A. Angell, andW. Brooks: Diuretic activity of three primary fractions of total nondialyzable solids from human urine. Proc. Soc. exp. Biol. (N.Y.)111, 316 (1962).

    Google Scholar 

  • McDonald, S. J., andH. E. de Wardener: The relationship between renal arterial perfusion pressure and the increase in sodium excretion which occurs during an infusion of saline. Nephron,2, 1 (1965).

    Google Scholar 

  • Milies, E.: A new diuretic factor of hepatic origin. Acta physiol. lat.-americ.10, 178 (1960).

    Google Scholar 

  • Mills, I. H., H. E. de Wardener, C. J. Hayter, andW. F. Clapham: Studies on the afferent mechanism of the sodium chloride diuresis which follows the intravenous saline in the dog. Clin. Sci.21, 259 (1961).

    Google Scholar 

  • Priestley, J. G.: The regulation of excretion of water by the kidneys. J. Physiol. (Lond.)50, 304 (1916).

    Google Scholar 

  • Rector, jr. F. C., G. van Giesen, F. Kiil, andD. W. Seldin: Influence of expansion of extracellular volume on tubular reabsorption of sodium independent of changes in glomerular filtration rate and aldosterone activity. J. clin. Invest.43, 341 (1964).

    Google Scholar 

  • Roemmelt, J. C., O. W. Sartorius, andR. F. Pitts: Excretion and reabsorption of sodium and water in the adrenalectomized dog. Amer. J. Physiol.159, 124 (1949).

    Google Scholar 

  • Rovner, D. R., J. W. Conn, R. F. Knopf, E. L. Cohen, andM. T.-Y. Hsueh: Nature of renal escape from the sodium-retaining effect of aldosterone in primary aldosteronism and in normal subjects. J. clin. Endocr.25, 53 (1965).

    Google Scholar 

  • Stein, R. M., D. D. Bercovitch, andM. F. Levitt: Dual effects of saline loading on renal tubular sodium reabsorption in the dog. Amer. J. Physiol.207, 826 (1964).

    Google Scholar 

  • Strauss, M. B., R. K. Davis, J. D. Rosenbaum, andE. C. Rossmeisl: Production of increased renal sodium excretion by the hypotonic expansion of extracellular fluid volume in recumbent subjects. J. clin. Invest.31, 80 (1952).

    Google Scholar 

  • Strauss, M. B., E. Lamdin, W. B. Smith, andI. J. Bleifer: Surfait and deficit of sodium. Arch. intern. Med.102, 527 (1958).

    Google Scholar 

  • Thompson, W. H.: Diuretic effects of sodium chloride solutions. J. Physiol. (Lond.)25, 487 (1900).

    Google Scholar 

  • Toussaint, C., andP. Vereerstraeten: Renal tubular transport of sodium during sodium chloride and sodium bicarbonate loadings in the normal dogs. Experientia (Basel)16, 309 (1960).

    Google Scholar 

  • Wardener, H. E. de, I. H. Mills, W. F. Clapham, andC. J. Hayter: Studies on the efferent mechanism of the sodium diuresis which follows the administration of intravenous saline in the dog. Clin. Sci.21, 249 (1961).

    Google Scholar 

  • Welt, L. G., andJ. Orloff: The effects of an increase in plasma volume on the metabolism and excretion of water and electrolytes by normal subjects. J. clin. Invest.30, 751 (1951).

    Google Scholar 

  • Windhager, E. E., andG. Giebisch: Micropuncture study of renal tubular transfer of sodium chloride in the rat. Amer. J. Physiol.200, 581 (1961a);

    Google Scholar 

  • Comparison of short-circuit current and net water movement in single perfused proximal tubules of rat kidneys. Nature (Lond.)191, 1205 (1961b).

    Google Scholar 

  • Wrong, O.: The relationship between water retention and electrolyte excretion following administration of antidiuretic hormone. Clin. Sci.15, 401 (1956).

    Google Scholar 

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Krück, F., Ressel, C. & Selb, D. Biologischer Nachweis eines humoralen natriuretischen Prinzips im Urin gesunder Menschen. Klin Wochenschr 45, 30–34 (1967). https://doi.org/10.1007/BF01745735

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