Advertisement

Pflügers Archiv

, Volume 413, Issue 1, pp 62–66 | Cite as

A comparison of the effects of renal artery constriction and anemia on the production of erythropoietin

  • H. Pagel
  • W. Jelkmann
  • C. Weiss
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands

Abstract

It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.

Key words

Erythropoiesis Erythropoietin Renal artery constriction Hypoxia Kidney Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbrecht PH, Vander AJ, Turcotte JG (1969) Effects of saline loading on the renin, erythropoietin, and blood pressure responses to canine renal allotransplantation. Circ Res 25:99–105Google Scholar
  2. Bourgoignie JJ, Gallagher NI, Perry HM, Kurz L, Warnecke MA, Donati RM (1968) Renin and erythropoietin in normotensive and in hypertensive patients. J Lab Clin Med 71:523–536Google Scholar
  3. Cooper GW, Nocenti MR (1961) Unilateral renal ischemia and erythropoietin. Proc Soc Exp Biol Med 108:546–549.Google Scholar
  4. Cotes PM, Bangham DR (1961) Bioassay of erythropoietin in mice made polycythemic by exposure to air at reduced pressure. Nature 191:1065–1067Google Scholar
  5. Donati RM, Bourgoignie JJ, Kuhn C, Gallagher NI, Perry HM (1968) Dissociation of circulating renin and erythropoietin in rats. Circ Res 22:91–95Google Scholar
  6. Erslev AJ (1975) Renal biogenesis of erythropoietin. Am J Med 58:25–30Google Scholar
  7. Erslev AJ, Caro J, Kansu E, Silver R (1980) Renal and extrarenal erythropoietin production in anaemic rats. Br J Haematol 45:65–72Google Scholar
  8. Fink GD, Fisher JW (1977) Role of the sympathetic nervous system in the control of erythropoietin production. In: Fisher JW (ed) Kidney hormones, vol II, Erythropoietin. Academic Press, New York, pp 387–413Google Scholar
  9. Fisher JW (1983) Control of erythropoietin production. Proc Soc Exp Biol Med 173:289–305Google Scholar
  10. Fisher JW, Samuels AI (1967) Relationship between renal blood flow and erythropoietin production in dogs. Proc Soc Exp Biol Med 125:482–485Google Scholar
  11. Fisher JW, Schofield R, Porteous DD (1965) Effects of renal hypoxia on erythropoietin production. Br J Haematol 11:382–388Google Scholar
  12. Fried W (1975) Erythropoietin and the kidney. Nephron 15:327–349Google Scholar
  13. Gross DM, Mujovic VM, Jubiz W, Fisher JW (1976) Enhanced erythropoietin and prostaglandin E production in the dog following renal artery constriction. Proc Soc Exp Biol Med 151:498–501Google Scholar
  14. Hansen P (1964) Polycythaemia produced by constriction of the renal artery in a rabbit. Acta Pathol Microbiol Scand 60:465–472Google Scholar
  15. Hudgson P, Pearce JMS, Yeates WK (1967) Renal artery stenosis with hypertension and high haematocrit. Br Med J 1:18–21Google Scholar
  16. Jelkmann W (1986) Renal erythropoietin: properties and production. Rev Physiol Biochem Pharmacol 104:139–215Google Scholar
  17. Jelkmann W, Bauer C (1981) Demonstration of high levels of erythropoietin in rat kidneys following hypoxic hypoxia. Pflügers Arch 392:34–39Google Scholar
  18. Jelkmann W, Seidl J (1987) Dependence of erythropoietin production on blood oxygen affinity and hemoglobin concentration in rats. Biomed Biochim Acta 46:S304-S308Google Scholar
  19. Jelkmann W, Kurtz A, Bauer C (1986) In vitro production of erythropoietin. In: Fisher JW (ed) Kidney hormones, vol III. Academic Press, London, pp 559–583Google Scholar
  20. Kramer K, Deetjen P (1960) Beziehungen des O2-Verbrauchs der Niere zu Durchblutung und Glomerulusfiltrat bei Änderung des arteriellen Druckes. Pflügers Arch 271:782–796Google Scholar
  21. Lechermann B, Jelkmann W (1985) Erythropoietin production in normoxic and hypoxic rats with increased blood O2 affinity. Resp Physiol 60:1–8Google Scholar
  22. Malgor LA, Fisher JW (1970) Effects of testosterone on erythropoietin production in isolated perfused kidneys. Am J Physiol 218:1732–1736Google Scholar
  23. Mujovic VM, Fisher JW (1974) The effects of indomethacin on erythropoietin production in dogs following renal artery constriction. I. The possible role of prostaglandins in the generation of erythropoietin by the kidney. J Pharmacol Exp Ther 191:575–580Google Scholar
  24. Murphy GP, Mirand EA, Takita H, Schoonees R, Groenewald JH (1971) The effect of hypoxia and ischemia on erythropoietin and renin release in dogs. Invest Urol 8:521–525Google Scholar
  25. Pavlovic-Kentera V, Hall DP, Bragassa C, Lange RD (1965) Unilateral renal hypoxia and production of erythropoietin. J Lab Clin Med 65:577–588Google Scholar
  26. Pavlovic-Kentera V, Susic D, Milenkovic P, Biljanovic-Paunovic L (1980) Effects of prostaglandin synthetase inhibitors, salt overload and renomedullary dissection on the hypoxia stimulated erythropoietin production in rats. Exp Hematol 8 (Suppl 8):283–290Google Scholar
  27. Rasch D, Herrendörfer G, Boek J, Busch K (1978) Verfahrensbibliothek, Versuchsplanung und -auswertung. VEB Deutscher Landwirtschaftsverlag, Berlin, pp 408–410Google Scholar
  28. Schuster SJ, Wilson JH, Erslev AJ, Caro J (1987) Physiologic regulation and tissue localization of renal erythropoietin messenger RNA. Blood 70:316–318Google Scholar
  29. Takaku F, Hirashima K, Nakao K (1962) Studies on the mechanism of erythropoietin production. I. Effect of unilateral constriction of the renal artery. J Lab Clin Med 59:815–820Google Scholar
  30. Tarazi RC, Frohlich ED, Dustan HP, Gifford RW, Page IH (1966) Hypertension and high hematocrit. Am J Cardiol 18:855–858Google Scholar
  31. Thurau K (1961) Renal Na-reabsorption and O2-uptake in dogs during hypoxia and hydrochlorothiazide infusion. Proc Soc Exp Biol Med 106:714–717Google Scholar
  32. Varkarakis MJ, Mirand EA, Murphy GP (1976) The response of the juxtaglomerular apparatus to stimuli effecting renin or erythropoietin release in canine renal allografts. Invest Urol 13:366–371Google Scholar
  33. Woodson RD, Auerbach S (1982) Effect of increased oxygen affinity and anemia on cardiac output and its distribution. J Appl Physiol 53:1299–1306Google Scholar
  34. Zivný J, Kolc J, Málek P, Neuwirt J (1972) Renal ischaemia, hypoxic hypoxia and erythropoietin production. Scand J Haematol 9:470–476Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • H. Pagel
    • 1
  • W. Jelkmann
    • 1
  • C. Weiss
    • 1
  1. 1.Institut für PhysiologieMedizinische Universität zu LübeckLübeck 1Federal Republic of Germany

Personalised recommendations