Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Aug;92(2):1073–1079. doi: 10.1172/JCI116612

Altered renal kallikrein and renin gene expression in nephrotic rats and modulation by converting enzyme inhibition.

F N Hutchison 1, S K Webster 1, A A Jaffa 1
PMCID: PMC294948  PMID: 8349789

Abstract

Urinary kallikrein excretion (UKE) is decreased in rats with passive Heymann nephritis (PHN), but increases after converting enzyme inhibition (CEI). Although CEI potentiates bradykinin activity, neither the effect of CEI on kallikrein secretion nor the abnormal renal kallikrein metabolism in PHN has been examined previously. To determine the mechanism by which CEI increases UKE, normal rats and PHN received enalapril, 40 mg/kg per d orally for 4 d. UKE was 85% lower in PHN than in normals and increased in both groups after CEI, although UKE in PHN remained significantly less than in normals. Kallikrein mRNA was significantly lower in PHN compared to normals but not in PHN treated with CEI and did not change in normal rats. Renin mRNA was significantly lower in PHN, and was stimulated by CEI only in normals. Renal kallikrein and renin content were not different and were not altered by CEI. Both kallikrein and renin genes appear to be transcriptionally suppressed in rats with PHN and the depressed kallikrein mRNA levels can be reversed by CEI. The modest increase in UKE despite normalization of kallikrein mRNA after CEI suggests that there is also a posttranscriptional defect in synthesis and/or secretion of kallikrein.

Full text

PDF
1073

Images in this article

1075Image
on p.1075
1075Image
on p.1075
1076Image
on p.1076
1077Image
on p.1077
1077Image
on p.1077
1077Image
on p.1077

Selected References

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

  1. Anderson S., Rennke H. G., Brenner B. M. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986 Jun;77(6):1993–2000. doi: 10.1172/JCI112528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antonaccio M. J. Angiotensin converting enzyme (ACE) inhibitors. Annu Rev Pharmacol Toxicol. 1982;22:57–87. doi: 10.1146/annurev.pa.22.040182.000421. [DOI] [PubMed] [Google Scholar]
  3. Bascands J. L., Pécher C., Cabos G., Girolami J. P. B2-kinin receptor like binding in rat glomerular membranes. Biochem Biophys Res Commun. 1989 Jan 16;158(1):99–104. doi: 10.1016/s0006-291x(89)80182-2. [DOI] [PubMed] [Google Scholar]
  4. Beierwaltes W. H., Prada J., Carretero O. A. Effect of glandular kallikrein on renin release in isolated rat glomeruli. Hypertension. 1985 Jan-Feb;7(1):27–31. doi: 10.1161/01.hyp.7.1.27. [DOI] [PubMed] [Google Scholar]
  5. Brady J. M., MacDonald R. J. The expression of two kallikrein gene family members in the rat kidney. Arch Biochem Biophys. 1990 May 1;278(2):342–349. doi: 10.1016/0003-9861(90)90269-5. [DOI] [PubMed] [Google Scholar]
  6. Burnham C. E., Hawelu-Johnson C. L., Frank B. M., Lynch K. R. Molecular cloning of rat renin cDNA and its gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5605–5609. doi: 10.1073/pnas.84.16.5605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Campbell D. J., Lawrence A. C., Towrie A., Kladis A., Valentijn A. J. Differential regulation of angiotensin peptide levels in plasma and kidney of the rat. Hypertension. 1991 Dec;18(6):763–773. doi: 10.1161/01.hyp.18.6.763. [DOI] [PubMed] [Google Scholar]
  8. Glasser R. J., Michael A. F. Urinary kallikrein in experimental renal disease. Lab Invest. 1976 Jun;34(6):616–622. [PubMed] [Google Scholar]
  9. Guimarães J. A., Vieira M. A., Camargo M. J., Maack T. Renal vasoconstrictive effect of kinins mediated by B1-kinin receptors. Eur J Pharmacol. 1986 Nov 4;130(3):177–185. doi: 10.1016/0014-2999(86)90266-9. [DOI] [PubMed] [Google Scholar]
  10. Hutchinson F. N., Schambelan M., Kaysen G. A. Modulation of albuminuria by dietary protein and converting enzyme inhibition. Am J Physiol. 1987 Oct;253(4 Pt 2):F719–F725. doi: 10.1152/ajprenal.1987.253.4.F719. [DOI] [PubMed] [Google Scholar]
  11. Hutchinson F. N., Webster S. K. Effect of ANG II receptor antagonist on albuminuria and renal function in passive Heymann nephritis. Am J Physiol. 1992 Aug;263(2 Pt 2):F311–F318. doi: 10.1152/ajprenal.1992.263.2.F311. [DOI] [PubMed] [Google Scholar]
  12. Hutchison F. N., Martin V. I. Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome. Am J Physiol. 1990 May;258(5 Pt 2):F1237–F1244. doi: 10.1152/ajprenal.1990.258.5.F1237. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. MacDonald R. J., Margolius H. S., Erdös E. G. Molecular biology of tissue kallikrein. Biochem J. 1988 Jul 15;253(2):313–321. doi: 10.1042/bj2530313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mayfield R. K., Margolius H. S. Renal kallikrein-kinin system. Relation to renal function and blood pressure. Am J Nephrol. 1983 Mar-Jun;3(2-3):145–155. doi: 10.1159/000166704. [DOI] [PubMed] [Google Scholar]
  17. Naftilan A. J., Oparil S. Effects of sodium intake and Goldblatt hypertension on renin release in rat kidney slices. Am J Physiol. 1981 Jun;240(6):F501–F507. doi: 10.1152/ajprenal.1981.240.6.F501. [DOI] [PubMed] [Google Scholar]
  18. Nakamura K., Kazama M., Morioka M., Tahara C., Abe T. Mechanism and significance of kinin formation in nephrotic syndrome. Adv Exp Med Biol. 1986;198(Pt B):253–262. doi: 10.1007/978-1-4757-0154-8_31. [DOI] [PubMed] [Google Scholar]
  19. Overlack A., Stumpe K. O., Kühnert M., Heck I. Altered blood pressure and renin responses to converting enzyme inhibition after aprotinin-induced kallikrein-kinin-system blockade. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):129s–132s. doi: 10.1042/cs059129s. [DOI] [PubMed] [Google Scholar]
  20. Salant D. J., Cybulsky A. V. Experimental glomerulonephritis. Methods Enzymol. 1988;162:421–461. doi: 10.1016/0076-6879(88)62096-9. [DOI] [PubMed] [Google Scholar]
  21. Sealey J. E., Atlas S. A., Laragh J. H., Oza N. B., Ryan J. W. Human urinary kallikrein converts inactive to active renin and is a possible physiological activator of renin. Nature. 1978 Sep 14;275(5676):144–145. doi: 10.1038/275144a0. [DOI] [PubMed] [Google Scholar]
  22. Shimamoto K., Margolius H. S., Chao J., Crosswell A. R. A direct radioimmunoassay of rat urinary kallikrein and comparison with other measures of urinary kallikrein activity. J Lab Clin Med. 1979 Jul;94(1):172–179. [PubMed] [Google Scholar]
  23. Tomita K., Pisano J. J. Binding of [3H]bradykinin in isolated nephron segments of the rabbit. Am J Physiol. 1984 May;246(5 Pt 2):F732–F737. doi: 10.1152/ajprenal.1984.246.5.F732. [DOI] [PubMed] [Google Scholar]
  24. Ura N., Carretero O. A., Erdös E. G. Role of renal endopeptidase 24.11 in kinin metabolism in vitro and in vivo. Kidney Int. 1987 Oct;32(4):507–513. doi: 10.1038/ki.1987.239. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES