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. 1992 May;89(5):1460–1468. doi: 10.1172/JCI115736

Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and hyperfiltration in the rat.

A A Jaffa 1, C P Vio 1, R H Silva 1, R J Vavrek 1, J M Stewart 1, P F Rust 1, R K Mayfield 1
PMCID: PMC443016  PMID: 1373739

Abstract

This study examined the role of tissue kallikrein and kinins in renal vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced total renal vascular resistance and increased glomerular filtration rate (GFR) by 25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated with a two- to threefold increase in urinary kinin excretion rate. Acute treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the rise in urinary kinins and prevented significant increases in GFR and RPF in response to AA. In a second group of rats pretreated with a B2 kinin receptor antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary kinins identically as in untreated controls, but GFR and RPF responses were absent. Aprotinin or the kinin antagonist produced no consistent change in renal function in rats that were not infused with AA.AA-induced increases in kinins were not associated with an increase in renal kallikrein activity. Notably, tissue active kallikrein level fell 50% in AA-infused rats. These studies provide evidence that kinins generated in the kidney participate in mediating renal vasodilation during acute infusion of AA.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ando T., Chao J., Chao L., Margolius H. S. An improved method for the measurement of rat tissue kallikrein using a monoclonal antibody which recognizes only active enzyme. Adv Exp Med Biol. 1986;198(Pt B):515–522. doi: 10.1007/978-1-4757-0154-8_65. [DOI] [PubMed] [Google Scholar]
  2. Barajas L., Powers K., Carretero O., Scicli A. G., Inagami T. Immunocytochemical localization of renin and kallikrein in the rat renal cortex. Kidney Int. 1986 May;29(5):965–970. doi: 10.1038/ki.1986.94. [DOI] [PubMed] [Google Scholar]
  3. Baylis C., Deen W. M., Myers B. D., Brenner B. M. Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex. Am J Physiol. 1976 Apr;230(4):1148–1158. doi: 10.1152/ajplegacy.1976.230.4.1148. [DOI] [PubMed] [Google Scholar]
  4. Baylis C. Effect of amino acid infusion as an index of renal vasodilatory capacity in pregnant rats. Am J Physiol. 1988 May;254(5 Pt 2):F650–F656. doi: 10.1152/ajprenal.1988.254.5.F650. [DOI] [PubMed] [Google Scholar]
  5. Beaven V. H., Pierce J. V., Pisano J. J. A sensitive isotopic procedure for the assay of esterase activity: measurement of human urinary kallikrein. Clin Chim Acta. 1971 Mar;32(1):67–73. doi: 10.1016/0009-8981(71)90465-7. [DOI] [PubMed] [Google Scholar]
  6. Beierwaltes W. H., Carretero O. A., Scicli A. G. Renal hemodynamics in response to a kinin analogue antagonist. Am J Physiol. 1988 Sep;255(3 Pt 2):F408–F414. doi: 10.1152/ajprenal.1988.255.3.F408. [DOI] [PubMed] [Google Scholar]
  7. Benigni A., Zoja C., Remuzzi A., Orisio S., Piccinelli A., Remuzzi G. Role of renal prostaglandins in normal and nephrotic rats with diet-induced hyperfiltration. J Lab Clin Med. 1986 Sep;108(3):230–240. [PubMed] [Google Scholar]
  8. Bolin P., Jaffa A. A., Rust P. F., Mayfield R. K. Acute and chronic responses of human renal kallikrein and kinins to dietary protein. Am J Physiol. 1989 Nov;257(5 Pt 2):F718–F723. doi: 10.1152/ajprenal.1989.257.5.F718. [DOI] [PubMed] [Google Scholar]
  9. Castellino P., Hunt W., DeFronzo R. A. Regulation of renal hemodynamics by plasma amino acid and hormone concentrations. Kidney Int Suppl. 1987 Oct;22:S15–S20. [PubMed] [Google Scholar]
  10. Chagnac A., Gafter U., Zevin D., Hirsch Y., Markovitz I., Levi J. Enalapril attenuates glomerular hyperfiltration following a meat meal. Nephron. 1989;51(4):466–469. doi: 10.1159/000185377. [DOI] [PubMed] [Google Scholar]
  11. Chao J., Margolius H. S. Studies on rat renal cortical cell kallikrein. II. Identification of kallikrein as an ecto-enzyme. Biochim Biophys Acta. 1979 Oct 11;570(2):330–340. doi: 10.1016/0005-2744(79)90153-0. [DOI] [PubMed] [Google Scholar]
  12. Corman B., Michel J. B. Interdependence of food intake and angiotensin converting enzyme inhibition on kidney function. J Hypertens Suppl. 1988 Dec;6(3):S65–S68. [PubMed] [Google Scholar]
  13. Daniels B. S., Hostetter T. H. Effects of dietary protein intake on vasoactive hormones. Am J Physiol. 1990 May;258(5 Pt 2):R1095–R1100. doi: 10.1152/ajpregu.1990.258.5.R1095. [DOI] [PubMed] [Google Scholar]
  14. DeFronzo R. A., Goldberg M., Agus Z. S. The effects of glucose and insulin on renal electrolyte transport. J Clin Invest. 1976 Jul;58(1):83–90. doi: 10.1172/JCI108463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Edwards R. M. Response of isolated renal arterioles to acetylcholine, dopamine, and bradykinin. Am J Physiol. 1985 Feb;248(2 Pt 2):F183–F189. doi: 10.1152/ajprenal.1985.248.2.F183. [DOI] [PubMed] [Google Scholar]
  16. Emond C., Bascands J. L., Cabos-Boutot G., Pecher C., Girolami J. P. Effect of changes in sodium or water intake on glomerular B2-kinin-binding sites. Am J Physiol. 1989 Sep;257(3 Pt 2):F353–F358. doi: 10.1152/ajprenal.1989.257.3.F353. [DOI] [PubMed] [Google Scholar]
  17. Fernández-Repollet E., Tapia E., Martínez-Maldonado M. Effects of angiotensin-converting enzyme inhibition on altered renal hemodynamics induced by low protein diet in the rat. J Clin Invest. 1987 Oct;80(4):1045–1049. doi: 10.1172/JCI113158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Figueroa C. D., MacIver A. G., Mackenzie J. C., Bhoola K. D. Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron. Histochemistry. 1988;89(5):437–442. doi: 10.1007/BF00492599. [DOI] [PubMed] [Google Scholar]
  19. Gardes J., Baussant T., Corvol P., Ménard J., Alhenc-Gelas F. Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II. Am J Physiol. 1990 May;258(5 Pt 2):F1273–F1281. doi: 10.1152/ajprenal.1990.258.5.F1273. [DOI] [PubMed] [Google Scholar]
  20. Herrera J., Rodríguez-Iturbe B., Parra G., Coello J., García R., Colina-Chourio J., Sinaiko A. Urinary prostaglandin E and kallikrein activity in glomerular hyperfiltration induced by a meat meal in man. Clin Nephrol. 1988 Sep;30(3):151–157. [PubMed] [Google Scholar]
  21. Hirschberg R. R., Zipser R. D., Slomowitz L. A., Kopple J. D. Glucagon and prostaglandins are mediators of amino acid-induced rise in renal hemodynamics. Kidney Int. 1988 Jun;33(6):1147–1155. doi: 10.1038/ki.1988.123. [DOI] [PubMed] [Google Scholar]
  22. Hirschberg R., Kopple J. D. Role of growth hormone in the amino acid-induced acute rise in renal function in man. Kidney Int. 1987 Sep;32(3):382–387. doi: 10.1038/ki.1987.221. [DOI] [PubMed] [Google Scholar]
  23. Hostetter T. H. Human renal response to meat meal. Am J Physiol. 1986 Apr;250(4 Pt 2):F613–F618. doi: 10.1152/ajprenal.1986.250.4.F613. [DOI] [PubMed] [Google Scholar]
  24. Hostetter T. H., Meyer T. W., Rennke H. G., Brenner B. M. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int. 1986 Oct;30(4):509–517. doi: 10.1038/ki.1986.215. [DOI] [PubMed] [Google Scholar]
  25. Hura C. E., Kunau R. T., Jr Angiotensin II-stimulated prostaglandin production by canine renal afferent arterioles. Am J Physiol. 1988 May;254(5 Pt 2):F734–F738. doi: 10.1152/ajprenal.1988.254.5.F734. [DOI] [PubMed] [Google Scholar]
  26. Jaffa A. A., Harvey J. N., Sutherland S. E., Margolius H. S., Mayfield R. K. Renal kallikrein responses to dietary protein: a possible mediator of hyperfiltration. Kidney Int. 1989 Dec;36(6):1003–1010. doi: 10.1038/ki.1989.294. [DOI] [PubMed] [Google Scholar]
  27. Jaffa A. A., Miller D. H., Bailey G. S., Chao J., Margolius H. S., Mayfield R. K. Abnormal regulation of renal kallikrein in experimental diabetes. Effects of insulin on prokallikrein synthesis and activation. J Clin Invest. 1987 Dec;80(6):1651–1659. doi: 10.1172/JCI113254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Krishna G. G., Newell G., Miller E., Heeger P., Smith R., Polansky M., Kapoor S., Hoeldtke R. Protein-induced glomerular hyperfiltration: role of hormonal factors. Kidney Int. 1988 Feb;33(2):578–583. doi: 10.1038/ki.1988.36. [DOI] [PubMed] [Google Scholar]
  29. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  30. Levine M. M., Kirschenbaum M. A., Chaudhari A., Wong M. W., Bricker N. S. Effect of protein on glomerular filtration rate and prostanoid synthesis in normal and uremic rats. Am J Physiol. 1986 Oct;251(4 Pt 2):F635–F641. doi: 10.1152/ajprenal.1986.251.4.F635. [DOI] [PubMed] [Google Scholar]
  31. Madeddu P., Glorioso N., Soro A., Manunta P., Troffa C., Tonolo G., Grazia Melis M., Pazzola A. Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats. Clin Sci (Lond) 1990 Feb;78(2):165–168. doi: 10.1042/cs0780165. [DOI] [PubMed] [Google Scholar]
  32. Mair M., Zhegu Z., Binder B. R. Hemodynamics of the isolated perfused rat kidney in the absence and presence of kallikrein substrate. Adv Exp Med Biol. 1986;198(Pt A):173–180. doi: 10.1007/978-1-4684-5143-6_24. [DOI] [PubMed] [Google Scholar]
  33. McCaa R. E. Studies in vivo with angiotensin I converting enzyme (kininase II) inhibitors. Fed Proc. 1979 Dec;38(13):2783–2787. [PubMed] [Google Scholar]
  34. Meyer T. W., Ichikawa I., Zatz R., Brenner B. M. The renal hemodynamic response to amino acid infusion in the rat. Trans Assoc Am Physicians. 1983;96:76–83. [PubMed] [Google Scholar]
  35. Nakagawa M., Stewart J. M., Vavrek R. J., Nasjletti A. Effects of a kinin antagonist on renal function in rats. Am J Physiol. 1990 Mar;258(3 Pt 2):F643–F648. doi: 10.1152/ajprenal.1990.258.3.F643. [DOI] [PubMed] [Google Scholar]
  36. Paller M. S., Hostetter T. H. Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II. Am J Physiol. 1986 Jul;251(1 Pt 2):F34–F39. doi: 10.1152/ajprenal.1986.251.1.F34. [DOI] [PubMed] [Google Scholar]
  37. Premen A. J., Hall J. E., Smith M. J., Jr Postprandial regulation of renal hemodynamics: role of pancreatic glucagon. Am J Physiol. 1985 May;248(5 Pt 2):F656–F662. doi: 10.1152/ajprenal.1985.248.5.F656. [DOI] [PubMed] [Google Scholar]
  38. Premen A. J. Nature of the renal hemodynamic action of amino acids in dogs. Am J Physiol. 1989 Apr;256(4 Pt 2):F516–F523. doi: 10.1152/ajprenal.1989.256.4.F516. [DOI] [PubMed] [Google Scholar]
  39. Premen A. J. Potential mechanisms mediating postprandial renal hyperemia and hyperfiltration. FASEB J. 1988 Feb;2(2):131–137. doi: 10.1096/fasebj.2.2.3277887. [DOI] [PubMed] [Google Scholar]
  40. Rosenberg M. E., Chmielewski D., Hostetter T. H. Effect of dietary protein on rat renin and angiotensinogen gene expression. J Clin Invest. 1990 Apr;85(4):1144–1149. doi: 10.1172/JCI114546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosenberg M. E., Swanson J. E., Thomas B. L., Hostetter T. H. Glomerular and hormonal responses to dietary protein intake in human renal disease. Am J Physiol. 1987 Dec;253(6 Pt 2):F1083–F1090. doi: 10.1152/ajprenal.1987.253.6.F1083. [DOI] [PubMed] [Google Scholar]
  42. Ruilope L. M., Rodicio J., Garcia Robles R., Sancho J., Miranda B., Granger J. P., Romero J. C. Influence of a low sodium diet on the renal response to amino acid infusions in humans. Kidney Int. 1987 Apr;31(4):992–999. doi: 10.1038/ki.1987.97. [DOI] [PubMed] [Google Scholar]
  43. Seino M., Abe K., Nushiro N., Omata K., Kasai Y., Yoshinaga K. Effects of a competitive antagonist of bradykinin on blood pressure and renal blood flow in anesthetized rats. J Hypertens. 1988 Nov;6(11):867–871. doi: 10.1097/00004872-198811000-00004. [DOI] [PubMed] [Google Scholar]
  44. Seto S., Kher V., Scicli A. G., Beierwaltes W. H., Carretero O. A. The effect of aprotinin (a serine protease inhibitor) on renal function and renin release. Hypertension. 1983 Nov-Dec;5(6):893–899. doi: 10.1161/01.hyp.5.6.893. [DOI] [PubMed] [Google Scholar]
  45. Shimamoto K., Ando T., Nakao T., Tanaka S., Sakuma M., Miyahara M. A sensitive radioimmunoassay method for urinary kinins in man. J Lab Clin Med. 1978 May;91(5):721–728. [PubMed] [Google Scholar]
  46. Tolins J. P., Raij L. Effects of amino acid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor. Hypertension. 1991 Jun;17(6 Pt 2):1045–1051. doi: 10.1161/01.hyp.17.6.1045. [DOI] [PubMed] [Google Scholar]
  47. Vio C. P., Figueroa C. D., Caorsi I. Anatomical relationship between kallikrein-containing tubules and the juxtaglomerular apparatus in the human kidney. Am J Hypertens. 1988 Jul;1(3 Pt 1):269–271. doi: 10.1093/ajh/1.3.269. [DOI] [PubMed] [Google Scholar]
  48. Vio C. P., Roa J. P., Silva R., Powers C. A. Localization of immunoreactive glandular kallikrein in lactotrophs of the rat anterior pituitary. Neuroendocrinology. 1990 Jan;51(1):10–14. doi: 10.1159/000125309. [DOI] [PubMed] [Google Scholar]
  49. Vío C. P., Figueroa C. D. Subcellular localization of renal kallikrein by ultrastructural immunocytochemistry. Kidney Int. 1985 Jul;28(1):36–42. doi: 10.1038/ki.1985.115. [DOI] [PubMed] [Google Scholar]
  50. Zatz R., Meyer T. W., Rennke H. G., Brenner B. M. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5963–5967. doi: 10.1073/pnas.82.17.5963. [DOI] [PMC free article] [PubMed] [Google Scholar]

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