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The effect of inhibition of prostaglandin synthesis on tubuloglomerular feedback in the rat kidney

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
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Abstract

To further clarify the mechanism mediating the reduction of nephron filtration rate in response to an increase of loop of Henle flow rate we have studied the effect of prostaglandin inhibition on tubuloglomerular feedback in rats. Following inravenous administration of 2 or 5 mg/kg indomethacin feedback responses expressed as the percent reduction of early proximal flow rate (EPFR) during flow elevation from 0–40 nl/min decreased from control values of −54.3±4.3% (mean ± S.E.) and −39.5±3.9% to −27.9±2.8% (P<0.001) and −5.0±4.9% (P<0.001) respectively. A significant reduction in the feedback response was also seen following intravenous administration of 2 or 5 mg/kg Ro 20-5720 (−28.8±5.8% and −7.8±3.8% respectively), 10 mg/kg meclofenamate (−15±4%), and 2 mg/kg eicosa-5,8,11,14-tetraynoic acid (−16.2±4.8%). In contrast to control animals injection of 5 mg/kg indomethacin had no effect on the feedback response in rats kept on a low salt diet. After applying a single dose of 5 mg/kg indomethacin or Ro 20-5720 feedback responses were reduced to −5.4±4.3% and −3.0±4.36% in the period 0–80 min, but were normal in the period 81–160 min after injection (−36.1±2.83% and −44.3±2.82% respectively). A dose dependent inhibition of the feedback response was also noted when indomethacin was applied intraluminally with full inhibition being established at a concentration of 0.5 mM. Urinary excretion rates of PGE2 and PGF2α fell from control values of 286.1±73.7 and 143.5±25.9 pg/min to 31.2±9.9 and 23.6±9 pg/min following 2 mg/kg indomethacin and to 36.8±4.4 and 8.9±1.9 pg/min following 5 mg/kg Ro 20-5720. Reduction of PG excretion was not reversible during the time of the experiment. Our results demonstrate a consistent decrease of tubuloglomerular feedback responses during inhibition of prostaglandin biosynthesis.

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References

  1. Baylis, C., Deen, W. M., Myers, B. D., Brenner, B. M.: Effects of some vasodilator drugs on transcapillary fluid exchanges in renal cortex. Am. J. Physiol.230, 1148–1158 (1976)

    Google Scholar 

  2. Bito, L. Z.: Inhibition of renal prostaglandin metabolism and excretion by probenecid, bromcresol green and indomethacin. Prostaglandins12, 639–646 (1976)

    Google Scholar 

  3. Bolger, P. M., Eisner, G. M., Ramwell, P. W., Slotkoff, L. M.: Effect of prostaglandin synthesis on renal function and renin in the dog. Nature259, 244–245 (1976)

    Google Scholar 

  4. Briggs, J. P., Wright, F. S.: Feedback control of glomerular filtration rate: site of the effector mechanism. Kidney Int.12, 552 (1977)

    Google Scholar 

  5. Burke, T. J., Navar, L. G., Clapp, J. R., Robinson, R. R.: Response of single nephron glomerular filtration rate to distal nephron microperfusion. Kidney Int.6, 230–240 (1974)

    Google Scholar 

  6. Dunham, E. W.: Effects of prostaglandins on renal blood flow in the rat. Fed. Proc.35, 223 (1976)

    Google Scholar 

  7. Dunn, M. J., Hood, V. L.: Prostaglandins and the kidney. Am. J. Physiol.233, F 169-F 184 (1977)

    Google Scholar 

  8. Flower, R. J.: Drugs which inhibit prostaglandin biosynthesis. Pharmacol. Rev.26, 33–67 (1974)

    Google Scholar 

  9. Frölich, J. C., Wilson, T. W., Sweetman, B. J., Smigel, M., Nies, A. S., Carr, K., Watson, J. T., Oates, J. A.: Urinary prostaglandins. Identification and origin. J. Clin. Invest.55, 763–770 (1975)

    Google Scholar 

  10. Hamberg, M.: Inhibition of prostaglandin synthesis in man. Biochem. Biophys. Res. Commun.49, 720–726 (1972)

    Google Scholar 

  11. Higashihara, E., Kokko, J.: The response of superficial and juxtamedullary glomerular filtration rates to prostaglandin inhibition. Abstracts VII. Int. Congr. Nephrol., Q-3, Montreal (1978)

  12. Hierholzer, K., Müller-Suur, R., Gutsche, H.-U., Butz, M., Lichtenstein, I.: Filtration in surface glomeruli as regulated by flow rate through the loop of Henle. Pflügers Arch.352, 315–337 (1974)

    Google Scholar 

  13. Hon, J. W.: Inhibition of multiple cyclic nucleotide phosphodiesterase by indomethacin. Tex. Rep. Biol. Med.31, 574 (1973)

    Google Scholar 

  14. Hon, J. W., Kauffman, F. C.: Inhibition of cyclic nucleotide phosphodiesterase by indomethacin. Pharmacologist16, 330 (1974)

    Google Scholar 

  15. Horrobin, D. F., Manku, M. S., Franks, D. J., Hamet, P.: Methylxanthine phosphodiesterase inhibitors behave as prostaglandin antagonists in a perfused rat mesenteric artery preparation. Prostaglandins13, 33–40 (1977)

    Google Scholar 

  16. Kirschenbaum, M. A., Stein, J. H.: Effect of inhibition of prostaglandin synthesis on urinary sodium excretion in conscious dogs. J. Clin. Invest.57, 517–521 (1976)

    Google Scholar 

  17. Larsson, C., Änggård, E.: Regional differences in the formation and metabolism of prostaglandins in the rabbit kidney. Eur. J. Pharmacol.21, 30–36 (1973)

    Google Scholar 

  18. Larsson, C., Weber, P., Änggård, E.: Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit. Eur. J. Pharmacol.28, 391–394 (1974)

    Google Scholar 

  19. Malik, K. U., McGiff, J. C.: Modulation by prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney. Circ. Res.36, 599–609 (1975)

    Google Scholar 

  20. Manku, M. S., Horrobin, D. F.: Indomethacin inhibits responses to all vasoconstrictors in rat mesenteric vascular bed restoration of responses by prostaglandin E2. Prostaglandins12, 369–376 (1976)

    Google Scholar 

  21. McGiff, J. C., Malik, K. U., Terragno, N. A.: Prostaglandins as determinants of vascular reactivity. Fed. Proc.35, 2382–2387 (1976)

    Google Scholar 

  22. Newcombe, D. S., Thanassi, N. M., Ciosek, C. P.: Cartilage cyclic nucleotide phosphodiesterase: inhibition by antiinflammatory agents. Life Sci.14, 505–519 (1974)

    Google Scholar 

  23. Northover, B. J.: Mechanism of the inhibiting action of indomethacin on smooth muscle. Br. J. Pharmacol.41, 540–551 (1971)

    Google Scholar 

  24. Ploth, D. W., Schnermann, J., Dahlheim, H., Hermle, M., Schmidmeier, E.: Autoregulation and tubuloglomerular feedback in normotensive and hypertensive rats. Kidney Int.12, 253–267 (1977)

    Google Scholar 

  25. Ramsay, J. A., Brown, R. H. J., Croghan, P. C.: Electrometric titration of chloride in small volumes. J. Exp. Biol.32, 822–829 (1955)

    Google Scholar 

  26. Rennick, B. R.: Renal tubular transport of prostaglandins: inhibition by probenecid and indomethacin. Am. J. Physiol.233, F 133-F 137 (1977)

    Google Scholar 

  27. Scherer, B., Schnermann, J., Sofroniev, M., Weber, P. C.: Prostaglandin (PG) analysis in urine of humans and rats by different radioimmunoassays — effect on PG-excretion by PG-synthetase inhibitors, laparatomy and furosemide. Prostaglandins15, 255–266 (1978)

    Google Scholar 

  28. Schnermann, J., Hermle, M.: Maintenance of feedback regulation of filtration dynamics in the absence of divalent cations in the lumen of the distal tubule. Pflügers Arch.358, 311–323 (1975)

    Google Scholar 

  29. Schnermann, J., Wright, F. S., Davis, J. M., Stackelberg, W. v., Grill, G.: Regulation of superficial nephron filtration rate by tubulo-glomerular feedback. Pflügers Arch.318, 147–175 (1970)

    Google Scholar 

  30. Schnermann, J., Davis, J. M., Wunderlich, P., Levine, D. Z., Horster, M.: Technical problems in the micropuncture determination of nephron filtration rate and their functional implications. Pflügers Arch.329, 307–320 (1971)

    Google Scholar 

  31. Schnermann, J., Hermle, M., Schmidmeier, E., Dahlheim, H.: Impaired potency for feedback regulation of glomerular filtration rate in DOCA escaped rats. Pflügers Arch.358, 325–338 (1975)

    Google Scholar 

  32. Schnermann, J., Ploth, D. W., Hermle, M.: Activation of tubuloglomerular feedback by chloride transport. Pflügers Arch.362, 229–240 (1976)

    Google Scholar 

  33. Schnermann, J., Osswald, H., Hermle, M.: Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Pflügers Arch.369, 39–48 (1977)

    Google Scholar 

  34. Smith, W. L., Bell, T. G.: Immunohistochemical localization of prostaglandin-forming cyclooxygenase in mammalian renal cortex. Prostaglandins15, 715 (1978)

    Google Scholar 

  35. Spector, D., Zusman, R. M., Caldwell, B. V., Speroff, L.: The distribution of prostaglandins A, E, and F in the human kidney. Prostaglandins6, 263–270 (1974)

    Google Scholar 

  36. Stefanovich, V.: Inhibition of 3′,5′-cyclic AMP phosphodiesterase with antiinflamamatory agents. Res. Comm. Chem. Pathol. Pharmacol.7, 573–582 (1974)

    Google Scholar 

  37. Thurau, K., Schnermann, J.: Die Natriumkonzentration an den Macula densa-Zellen als regulierender Faktor für das Glomerulumfiltrat (Mikropunktionsversuche). Klin. Wochenschr.43, 410–413 (1965)

    Google Scholar 

  38. Thurau, K., Dahlheim, H., Grüner, A., Mason, J., Granger, P.: Activation of renin in the single juxtaglomerular apparatus by sodium chloride in the tubular fluid at the macula densa. Circ. Res.31, II 182–186 (1972)

    Google Scholar 

  39. Vogt, W.: Role of phospholipase A2 in prostaglandin formation. In: Advances in Prostaglandin and Thromboxane Research (C. Galli et al., eds.), Vol. 3, pp. 89–95. New York: Raven Press 1978

    Google Scholar 

  40. Weber, P. C., Holzgreve, H., Stephan, R., Herbst, R.: Plasma renin activity and renal sodium and water excretion following infusion of arachidonic acid in rats. Eur. J. Pharmacol.34, 299–304 (1975)

    Google Scholar 

  41. Weber, P. C., Larsson, C., Änggård, E., Hamberg, M., Corey, E. J., Nicolaou, K. C., Samuelsson, B.: Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxydes. Circ. Res.39, 868–874 (1976)

    Google Scholar 

  42. Werning, C., Vetter, W., Weidmann, P., Schweikert, H. U., Stiel, D., Siegenthaler, W.: Effect of prostaglandin E1 on renin in the dog. Am. J. Physiol.220, 852–856 (1971)

    Google Scholar 

  43. Williams, W. M., Frölich, J. C., Nies, A. S., Oates, J. A.: Urinary prostaglandins: site of entry into renal tubular fluid. Kidney Int.11, 256–260 (1977)

    Google Scholar 

  44. Yun, J., Kelly, G., Bartter, F. C., Smith, H.: Role of prostaglandins in the control of renin secretion in the dog. Circ. Res.40, 459–464 (1977)

    Google Scholar 

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Authors and Affiliations

  1. Physiologisches Institut der Universität München, Pettenkoferstrasse 12, D-8000, München, Federal Republic of Germany

    J. Schnermann, G. Schubert & M. Hermle

  2. Medizinische Klinik Innenstadt der Universität München, Federal Republic of Germany

    R. Herbst & P. C. Weber

  3. Cleveland Clinic Research Division, Cleveland, Ohio, USA

    N. T. Stowe & S. Yarimizu

Authors
  1. J. Schnermann
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  2. G. Schubert
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  3. M. Hermle
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  4. R. Herbst
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  5. N. T. Stowe
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  6. S. Yarimizu
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  7. P. C. Weber
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Schnermann, J., Schubert, G., Hermle, M. et al. The effect of inhibition of prostaglandin synthesis on tubuloglomerular feedback in the rat kidney. Pflugers Arch. 379, 269–279 (1979). https://doi.org/10.1007/BF00581431

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  • DOI: https://doi.org/10.1007/BF00581431

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