Laboratory Investigation

Kidney International (1977) 11, 93–105; doi:10.1038/ki.1977.14

Urine-reinfusion natriuresis: Evidence for potent natriuretic factors in rat urine

Robert H Harris1 and William E Yarger1

1Veterans Administration Hospital and the Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina

Correspondence: Dr R H Harris, Box 3014, Duke University Medical Center, Durham, N.C. 27710, U.S.A.

Received 24 May 1976; Revised 17 September 1976.

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Abstract

Urine-reinfusion natriuresis: Evidence for potent natriuretic factors in rat urine. In awake rats the entire urine output was continuously reinfused i.v. Urine-reinfusion (UR) consistently led to the appearance, within one to two hours, of massive, sustained natriuresis and diuresis, suggesting the existence of potent natriuretic factors in the urine. At the time of maximal natriuresis, mean sodium excretion rate and urine flow rate were 25 and 15 times their respective values in control rats. This "urine-reinfusion natriuresis" could be demonstrated despite treatment with desoxycorticosterone acetate, blockage of prostaglandin synthesis by indomethacin or meclofenamate, reduction of plasma urea by pretreatment with a protein-free diet, or heating the urine to 100°C. The natriuresis was not prevented by the absence of vasopressin (in Brattleboro rats) and was augmented by vasopressin infusion. In the Brattleboro rats, a marked increase in (CH2O + CNa)/GFR with only a slight rise in CH2O/GFR during UR suggests inhibition of both proximal and distal tubular reabsorption. Renal blood flow and plasma flow increased markedly during UR with a lesser rise in GFR, consistent with post-glomerular vasodilatation. Thus, the phenomenon of urine-reinfusion natriuresis suggests the presence in rat urine of potent, heat-stable natriuretic factors, whose action is largely independent of changes in mineralocorticoids, prostaglandins, urea, or vasopressin. Renal vasodilatation, with decreased sodium reabsorption at both proximal and distal nephron sites, appears to play an important role in the natriuresis.

Natriurèse au cours de la réinjection d'urine: Preuve de l'existence de facteurs natriurétique et diurétique puissants dans Purine de rat. La totalité du débit urinaire a été réinjectée en continu chez des rats éveillés. La réinfusion d'urine (UR) détermine l'apparition, dans un délai d'une à deux heures, d'une natriurèse et d'une diurèse massive ce qui suggère la présence, dans l'urine, de facteurs natriurétiques puissants. Au moment de la natriurèse maximale les débits de sodium et d'urine sont égaux à 25 et 15 fois leurs valeurs respectives chez les animaux contrôles. Cette natriurèse par réinfusion d'urine peut être obtenue malgré le traitment par l'acétate de désoxycorticostérone, le blocage de la synthèse des prostaglandines par l'indométhacine, la diminution de l'urée plasmatique au moyen d'un prétraitement consistant en une alimentation sans protéines ou le chauffage de l'urine à 100° C. La natriurèse n'est pas empêchée par l'absence de vasopressine (rat Brattleboro), elle est augmentée par l'administration de vasopressine. Chez le rat Brattleboro une augmentation importante de (CH2O + CNa)/GFR avec une augmentation non significative de CH2O/GFR au cours de l'UR suggère l'inhibition de la réabsorption tubulaire proximale et distale. Les débits sanguin et plasmatique rénaux augmentent de façon importante au cours de l'UR cependant que le débit de filtration glomérulaire augmente moins, ce qui est compatible avec une vasodilatation post glomérulaire. Ainsi le phénomène de la natriurèse consécutive à la réinfusion d'urine suggère la présence, dans l'urine, d'un facteur natriurétique puissant, thermostable donc l'action est pour une grande part indépendante des modifications des minéralocorticoïdes, des prostaglandines, de l'urée et de la vasopressine. La vasodilatation rénale, qui diminue la réabsorption de sodium à la fois dans les régions proximale et distale du néphron, semble jouer un rôle important dans la natriurèse.

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References

  1. Sealey JE, Kirshman JD, Laragh JH: Natriuretic activity in plasma and urine of salt-loaded man and sheep. J. Clin Invest 48:2210–2224, 1969 | PubMed | ISI | ChemPort |
  2. Bourgoignie JJ, Hwang KH, Espinel C, Klahr S, Bricker NS: A natriuretic factor in the serum of patients with chronic uremia. J Clin Invest 51:1514–1527, 1972 | PubMed | ISI | ChemPort |
  3. Buckalew VM, Nelson DB: Natriuretic and sodium transport inhibitory activity in plasma of volume-expanded dogs. Kidney Int 5:12–22, 1974
  4. Brown PR, Koutsaimanis KG, DeWardener HE: Effect of urinary extracts from salt-loaded man on urinary sodium excretion by the rat. Kidney Int 2:1–5, 1973
  5. Bourgoignie JJ, Hwang KH, Ipakchi E, Bricker NS: The presence of a natriuretic factor in urine of patients with chronic uremia: The absence of the factor in nephrotic uremic patients. J Clin Invest 53:1559–1567, 1974
  6. Favre H, Hwang KH, Schmidt RW, Bricker NS, Bourgoignie JJ: An inhibitor of sodium transport in the urine of dogs with normal renal function. J Clin Invest 56:1302–1311, 1975 | PubMed | ISI | ChemPort |
  7. Gonick HC, Saldanha LF: A natriuretic principle derived from kidney tissue of volume-expanded rats. J Clin Invest 56:247–255, 1975
  8. Harris RH, Yarger WE: The pathogenesis of post-obstructive diuresis: The role of circulating natriuretic and diuretic factors, including urea. J Clin Invest 56:880–887, 1975 | PubMed | ISI | ChemPort |
  9. Harris RH, Yarger WE: Massive natriuresis and diuresis due to humoral factors in urine (abstr.). Clin Res 22:531A, 1974
  10. Harris RH, Yarger WE: "Urine-reinfusion natriuresis": The influences of sodium load, urea, ADH and mineralocorticoid (abstr.). Clin Res 23:36A, 1975
  11. Valtin H, Schroeder HA: Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). Am J Physiol 206:425–430, 1964 | PubMed | ISI | ChemPort |
  12. Harris RH, Yarger WE: Renal function after release of unilateral ureteral obstruction in rats. Am J Physiol 227:806–815, 1974
  13. Fawcett JK, Scott JE: A rapid and precise method for the determination of urea. J Clin Pathol 13:156–159, 1960
  14. Pitts RF: Physiology of the Kidney and Body Fluids (3rd ed). Chicago, Year Book Medical Publishers, Inc., 1974, p. 159
  15. Steel RGD, Torrie JH: Principles and Procedures of Statistics. New York, McGraw-Hill Book Company, Inc., 1969, p. 99–131
  16. Stein RM, Abramson RG, Bercovitch DD, Levitt MF: Effects of unilateral renal arterial constriction on tubular reabsorption of sodium and water during an osmotic diuresis. J Clin Invest 44:1720–1729, 1965
  17. Brenner B, Troy JL, Daugharty TM, Deen WM, Robertson CR: Dynamics of glomerular ultrafiltration in the rat: II. Plasma-flow dependence of GFR. Am J Physiol 223:1184–1190, 1972 | PubMed | ISI | ChemPort |
  18. Earley LE, Friedler RM: The effects of combined renal vasodilatation and pressor agents on renal hemodynamics and the tubular reabsorption of sodium. J Clin Invest 45:542–551, 1966
  19. Nissen OI: The extraction fraction of p-aminohippurate in the superficial and deep venous drainage area of the cat kidney. Acta Physiol Scand 73:329–338, 1968
  20. Velasquez MT, Notargiacomo AV, Cohn JN: Influence of cortical plasma transit-time on p-aminohippurate extraction during induced renal vasodilatation in anesthetized dogs. Clin Sci 43:401–411, 1972
  21. Orringer EP, Weiss FR, Preuss HG: Azotaemic inhibition of organic anion transport in the kidney of the rat: Mechanism and characteristics. Clin Sci 40:159–169, 1971
  22. Boumendil-Podevin EF, Podevin RA, Richet G: Uricosuric agents in uremic sera: Identification of indoxyl sulfate and hippuric acid. J Clin Invest 55:1142–1152, 1975 | PubMed | ChemPort |
  23. McNay JL, Rosello S, Dayton PG: Effects of azotemia on renal extraction and clearance of PAH and TEA. Am J Physiol 230:901–906, 1976
  24. Weber H, Bourgoignie JJ, Bricker NS: Effects of the natriuretic serum fraction on proximal tubular sodium reabsorption. Am J Physiol 226:419–425, 1974
  25. Brenner BM, Troy JL: Postglomerular vascular protein concentration: Evidence for a causal role in governing fluid reabsorption and glomerulotubular balance by the renal proximal tubule. J Clin Invest 50:336–349, 1971
  26. Green R, Windhager EE, Giebisch G: Protein oncotic pressure effects on proximal tubular fluid movement in the rat. Am J Physiol 226:265–276, 1974
  27. Grantham JJ, Qualizza PB, Welling LW: Influence of serum proteins on net fluid reabsorption of isolated proximal tubules. Kidney Int 2:66–75, 1972
  28. Imai M, Kokko JP: Transtubular oncotic pressure gradients and net fluid transport in isolated proximal tubules. Kidney Int 6:138–145, 1974
  29. Koch KM, Aynedjian HS, Bank N: Effect of acute hypertension on sodium reabsorption by the proximal tubule. J Clin Invest 47:1696–1709, 1968
  30. Buckalew VM, Puschett JB, Kintzel JE, Goldberg M: Mechanism of exaggerated natriuresis in hypertensive man: Impaired sodium transport in the loop of Henle. J Clin Invest 48:1007–1016, 1969
  31. Selkurt EE, Womack I, Dailey WN: Mechanism of natriuresis and diuresis during elevated renal arterial pressure. Am J Physiol 209:95–99, 1965
  32. Wesson LG Jr, Anslow WP Jr: Excretion of sodium and water during osmotic diuresis in the dog. Am J Physiol 153:465–474, 1948
  33. Thorn GK, Stein KE: Pitressin tannate therapy in diabetes insipidus. J Clin Endocrinol Metab 1:680–687, 1941
  34. Humphreys MH, Friedler RM, Earley LE: Natriuresis produced by vasopressin or hemorrhage during water diuresis in the dog. Am J Physiol 219:658–665, 1970
  35. Kurtzman NA, Rogers PW, Boonjarern S, Arruda JAL: Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion. Am J Physiol 228:890–894, 1975
  36. Fressinaud P, Corvol P, Menard J: Radioimmunoassay of urinary antidiuretic hormone in man: Stimulation-suppression tests. Kidney Int 6:184–190, 1974
  37. Wallin JD, Barratt LJ, Rector FC Jr, Seldin DW: The influence of flow rate and chloride delivery on TcH2O formation in the rat. Kidney Int 3:282–290, 1973
  38. Vander AJ: Direct effects of prostaglandin on renal function and renin release in anesthetized dog. Am J Physiol 214:218–221, 1968 | PubMed | ChemPort |
  39. Johnston HH, Herzog JP, Lauler DP: Effect of prostaglandin E1 on renal hemodynamics, sodium and water excretion. Am J Physiol 213:939–946, 1967 | PubMed | ChemPort |
  40. Venuto RC, O'Dorisio T, Ferris TF, Stein JH: Prostaglandins and renal function: II. The effect of prostaglandin inhibition on blood flow in the intact kidney of the dog. Prostaglandins 9:817–828, 1975
  41. Herbaczynska-Cedro K, Vane JR: Contribution of intrarenal generation of prostaglandin to autoregulation of renal blood flow in the dog. Circ Res 33:438–436, 1973
  42. Somova L: Inhibition of prostaglandin synthesis in the kidneys by aspirinlike drugs, in Advances in the Biosciences (suppl.), International Conference on Prostaglandins, Vienna, edited by Bergstrom S, Bernhard S, Braunschweig, Viewig, Pergamon Press, 1973, vol. 9, p. 335
  43. Romero JC, Dunlap CL, Strong CG: The effect of indomethacin and other anti-inflammatory drugs on the reninangiotensin system. J Clin Invest 58:282–288, 1976
  44. Schmidt RW, Bourgoignie JJ, Bricker NS: On the adaption in sodium excretion in chronic uremia: The effects of "proportional reduction" of sodium intake. J Clin Invest 53:1736–1741, 1974
  45. Emmanouel DS, Lindheimer MD, Katz AI: Mechanism of impaired water excretion in the hypothyroid rat. J Clin Invest 54:926–934, 1974 | PubMed | ChemPort |

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