Laboratory Investigation

Kidney International (1984) 26, 112–121; doi:10.1038/ki.1984.144

Effect of furosemide administration on glomerular and tubular dynamics in the rat

Bryan J Tucker1 and Roland C Blantz2

  1. 1University of California, San Diego
  2. 2School of Medicine, and The Veterans Administration Medical Center, San Diego, California

Correspondence: B J Tucker, Nephrology Research (151), Veterans Administration Medical Center, 3350 La Jolla Village Drive, San Diego, California 92161, USA

Received 16 February 1983; Revised 22 December 1983.

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Abstract

Effect of furosemide administration on glomerular and tubular dynamics in the rat. Furosemide, a potent diuretic, has also been shown (1) to inhibit or reduce tubuloglomerular feedback activity, (2) act as a vasodilatory agent, and (3) exhibit a modest carbonic anhydrase inhibitory effect, which could potentially reduce proximal tubule reabsorption. If furosemide can inhibit tubuloglomerular feedback as well as cause vasodilation, then glomerular filtration rate (GFR) should increase through alterations in the dynamics of glomerular ultrafiltration. The effect of acute furosemide infusion (4 mg/kg of body wt per hour) on glomerular and tubular dynamics was examined in Munich-Wistar rats by two protocols: The first allowed a 3% volume depletion (based on body wt) to occur as a result of furosemide administration (group 1); the second allowed a complete replacement of volume after furosemide administration (group 2). The results demonstrated that when volume status was maintained after furosemide administration, the nephron filtration rate remained constant (35 plusminus 3 vs. 33 plusminus 2 nl/min, NS) despite a twofold increase in distal flow rate (5 plusminus 1 vs. 10 plusminus 1 nl/min, P < 0.01), indicating an inhibition or suppression of the tubuloglomerular feedback system. With either protocol, furosemide administration did not alter total nephron vascular resistance and nephron blood flow (190 plusminus 17 vs. 200 plusminus 15 ml/min); however, the afferent arteriolar resistance did decrease in rats in which volume status was maintained. Finally, with volume status maintained, we were not able to demonstrate a reduction in absolute proximal fluid reabsorption despite a 7 mm Hg increase in interstitial hydrostatic pressure (4 plusminus 1 to 11 plusminus 1 mm Hg, P < 0.01) and no compensatory increase in interstitial oncotic pressure. These data indicate that tubuloglomerular feedback was inhibited but that GFR was not increased. Major changes occurred in interstitial pressures and interstitial volume after furosemide administration, but absolute proximal reabsorption remained constant.

Effet de l'administration de furosémide sur la dynamique glomérulaire et tubulaire chez le rat. Le furosémide, un diurétique puissant, peut également (1) inhiber ou réduire l'activité du rétro-contrôle tubulo-glomérulaire, (2) se comporter comme un agent vasodilatateur, et (3) montrer un effet inhibiteur modeste de G anhydrase carbonique, qui pourrait réduire la réabsorption tubulaire proximale. Si le furosémide peut inhiber le rétro-contrôle tubulo-glomérulaire et entrainer une vasodilatation, alors le débit de filtration glomérulaire (GFR) devrait s'élever en raison des altérations de la dynamique de l'ultrafiltration glomérulaire. Les effets d'une perfusion aiguë de furosemide (4 mg/kg poids par hr) sur la dynamique glomérulaire et tubulaire ont été examinés grâce à deux protocoles chez des rats Munich-Wistar: déplétion de 3% du volume corporel par administration de furosémide (groupe 1), et correction complète de la volémie après furosémide (groupe 2). Les résultats démontrent que quand la volémie a été maintenue après administration de furosémide, la filtration néphronique restait constante (35 plusminus 3 contre 33 plusminus 2 nl/min, NS) malgré un doublement du débit distal (5 plusminus 1 contre 10 plusminus 1 nl/min, P < 0,01), ce qui indique une inhibition ou une suppression du système de rétro-contrôle tubulo-glomérulaire. Avec l'un ou l'autre protocole, l'administration de furosémide n'a altéré ni la résistance vasculaire totale néphronique ni le débit sanguin néphronique (190 plusminus 17 contre 200 plusminus 15 ml/min); de quelque manière la résistance arteriolare afférente a descendu chez les rats chez que la volémie était maintenue. Finalement, en maintenant la volémie, nous n'avons pas pu démontrer de réduction de la réabsorption proximale absolue de liquides malgré une élévation de 7 mm Hg de la pression hydrostatique interstitielle (de 4 plusminus 1 à 11 plusminus 1 mm Hg, P < 0,01), et l'absence d'élévation compensatrice de la pression oncotique interstitielle. Ces données indiquent que le rétro-contrôle tubulo-glomérulaire était inhibé mais que la filtration glomérulaire n'était pas augmentée. Modifications majeures se sont produites dans les pressions interstitielles et le volume interstitiel après administration de furosémide, mais la réabsorption proximale absolue est restée constante.

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References

  1. Wright FS, Schnermann J: Interference of feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide. J Clin Invest 53:1695–1708, 1974 | PubMed | ISI | ChemPort |
  2. Brunkhorst R, Müller-Ott K, Gutsche H-U, Niedermayer W: Effect of furosemide, bumetanide and piretanide on the sensor of the tubuloglomerular feedback mechanism. Proc Eur Dial Transplant Assoc 15:613–616, 1978
  3. Stein JH, Mauk RC, Boonjarern S, Ferris TF: Differences in the effect of furosemide and chlorothiazide on the distribution of renal cortical blood flow in the dog. J Lab Clin Med 79:995–1003, 1972
  4. Corsini WA, Hook JB, Bailie MD: Control of renin secretion in the dog: Effect of furosemide on vascular and macula densa receptors. Circ Res 37:464–470, 1975 | PubMed | ISI | ChemPort |
  5. Vander AJ, Carlson J: Mechanism of the effects of furosemide on renin secretion in anesthetized dogs. Circ Res 25:145–152, 1969
  6. Bailie MD, Davis LE, Loutzenhiser R: Intrarenal secretion in the dog: Effect of furosemide. Am J Physiol 224:425–430, 1973 | PubMed | ISI | ChemPort |
  7. Duchin KL, Peterson LN, Burke TJ: Effect of furosemide on renal autoregulation. Kidney Int 12:379–386, 1977
  8. Burke TJ, Duchin KL: Glomerular filtration during furosemide diuresis in the dog. Kidney Int 16:672–680, 1979
  9. Radtke HW, Rumrich G, Kinne-Saffran E, Ullrich KJ: Dual action of acetazolamide and furosemide on proximal volume absorption in the rat kidney. Kidney Int 1:100–105, 1972
  10. Stein JH, Wilson CB, Kirkendall WM: Differences in the acute effects of furosemide and ethacrynic acid in man. J Lab Clin Med 71:654–665, 1968
  11. Bonvalet JP, Menard J: Influence of furosemide and alpha-1-propranolol on glomerular filtration rate and renin secretion in the rat. Pfluegers Arch 346:107–119, 1974
  12. Brenner BM, Keimowitz RI, Wright FS, Berliner RW: An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest 48:290–300, 1969
  13. Blantz RC, Tucker BJ: Measurements of glomerular dynamics, in Methods of Pharmacology, Renal Pharmacology, edited by Martinez-Maldonado M, New York, Plenum, 1978, vol 4, pp 141–163
  14. Sterling K: Radioactive chromium technic for circulating red cell volume. Methods Med Res 8:69–76, 1960
  15. Sterling K, Gray SJ: The tagging of red blood cells and plasma protein with radioactive chromium. J Clin Invest 29:1604–1609, 1950 | PubMed | ISI | ChemPort |
  16. Intaglieta M, Pawula RF, Tompkins WR: Pressure measurements in the mammalian vasculature. Microvasc Res 2:212–220, 1970
  17. Blantz RC, Tucker BJ: Determinants of peritubular capillary fluid uptake in hydropenia and saline and plasma expansion. Am J Physiol 228:1927–1935, 1975
  18. Tucker BJ, Blantz RC: Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance. Am J Physiol 235:F142–F150, 1978
  19. Blantz RC, Tucker BJ, Gushwa L, Peterson OW: Mechanism of diuresis following acute modest hyperglycemia in the rat. Am J Physiol 244(13):F185–F194, 1983
  20. Wolgast M, Persson E, Schnermann J, Ulfendahl H, Wunderlich P: Colloid osmotic pressure of the subcapsular interstitial fluid of rat kidneys during hydropenia and volume expansion. Pfluegers Arch 340:123–131, 1973
  21. Brenner BM, Falchuk KH, Keimowitz RI, Berliner RW: The relationship between peritubular capillary protein concentration and fluid reabsorption by the renal proximal tubule. J Clin Invest 48:1519–1531, 1969
  22. Lowry OH, Rosenbrough NH, Fan AL, Randall RJ: Protein measurements with the Folin phenol reagent. J Biol Chem 193:265–275, 1951 | PubMed | ISI | ChemPort |
  23. Landis EM, Pappenheimer JR: Exchange of substances through capillary walls, in Handbook of Physiology, Section 2: Circulation, edited by Hamilton WF, Dow P, Washington, D.C., American Physiology Society, 1963, vol 2, pp 961–1034
  24. Hargens AR, Tucker BJ, Blantz RC: Renal lymph protein in the rat. Am J Physiol 233:F269–F273, 1977
  25. Blantz RC: Effect of mannitol on glomerular ultrafiltration in the hydropenic rat. J Clin Invest 54:1135–1143, 1974
  26. Tucker BJ, Blantz RC: An analysis of the determinants of nephron filtration rate. Am J Physiol 232:F477–F483, 1977 | PubMed | ISI | ChemPort |
  27. Tucker BJ, Blantz RC: Effects of glomerular filtration dynamics on the glomerular permeabilty coefficient. Am J Physiol 240:F245–F254, 1981 | PubMed | ISI | ChemPort |
  28. Wolgast M, Ulfendahl HR, Källskog O, Rasmussen N, Atkins JL, Pinter GG: Plasma protein distribution in kidney, in Protides of the Biological Fluids—21st Colloquium, edited by Peeters H, New York, Pergamon, 1973, pp 413–417
  29. Kömpf B, Karsunky K-P, Taugner R: Die Verteilung von J131-albumin in der niere von ratten und kaninchen. Pfluegers Arch 328:205–220, 1971
  30. Bliss CI: Statistics in Biology. New York, McGraw-Hill Book Co., 1970, pp 186–205
  31. Dunn OJ, Clark VA: Applied Statistics: Analysis of Variance and Regression. New York, Wiley, 1974, pp 221–304
  32. Kaufman JS, Hamburger RJ, Glamenbaum W: Tubuloglomerular feedback: Effect of dietary NaCl intake. Am J Physiol 231(6):1744–1749, 1976
  33. Ploth DW, Rudolph J, La Grange R, Navar LG: Tubuloglomerular feedback and single nephron function after converting enzyme inhibition in the rat. J Clin Invest 64:1325–1335, 1979
  34. Schnermann J, Ploth DW, Dahlheim H: Inter-relationship between autoregulation of glomerular filtration rate, tubuloglomerular feedback and juxtaglomerular renin activity in normotensive and hypertensive rats. Clin Sci Mol Med 51:1055–1075, 1976
  35. Tucker BJ, Steiner RW, Gushwa LC, Blantz RC: Studies on the tubulo-glomerular feedback system in the rat: The mechanism of reduction in filtration rate with benzolamide. J Clin Invest 62:933–1004, 1978
  36. Mason J, Kain H, Welsch J, Schnermann J: The early phase of experimental acute renal failure: VI. The influence of furosemide. Pfluegers Arch 392:125–133, 1981
  37. Burg M, Stoner L, Cardinal J, Green N: Furosemide effect on isolated perfused tubules. Am J Physiol 225(1):119–124, 1973 | PubMed | ISI | ChemPort |
  38. Schnermann J: Regulation of single nephron filtration rate by feedback: Facts and theories. Clin Nephrol 3:75–81, 1975
  39. Wright FS: Characteristics of feedback control of glomerular filtration rate. Fed Proc 40:87–92, 1981
  40. Kallskog O, Wolgast M: Driving forces over the peritubular capillary membrane in the rat kidney during antidiuresis and saline expansion. Acta Physiol Stand 89:116–125, 1973
  41. Quinn MD, Marsh DJ: Peritubular capillary control of proximal tubule reabsorption in the rat. Am J Physiol 236(5):F478–F487
  42. Wolgast M, Larson M, Nygren K: Functional characteristics of the renal interstitium. Am J Physiol 241:F105–F111, 1981 | PubMed |
  43. Ichikawa I, Brenner BM: Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat. J Clin Invest 65:1192–1201, 1980
  44. Brenner BM, Troy JL: Prostaglomerular 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
  45. Kon V, Troy JL, Ichikawa I: Effector loci for vasomotor control by renal nerves (abstract). Clin Res 30(2):454A, 1982
  46. Ichikawa I, Hoyer JR, Seiler MW, Brenner BM: Mechanism of glomerulotubular balance in the setting of heterogeneous glomerular injury. J Clin Invest 69:185–198, 1982 | PubMed | ISI |
  47. Larson M, Sjöquist M, Wolgast M: Renal interstitial volume of the rat kidney: Doctoral dissertation of M. Larson. Acta Universitatis Upsalinsis 380(2):1–23, 1981
  48. Tisher CC, Kokko JP: Relationship between peritubular oncotic pressure gradients and morphology in isolated proximal tubules. Kidney Int 2:66–75, 1972

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