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. 1992 Oct;90(4):1425–1435. doi: 10.1172/JCI116009

Renal tubular responsiveness to atrial natriuretic peptide in sodium-retaining chronic caval dogs. A possible role for kinins and luminal actions of the peptide.

L Legault 1, P Cernacek 1, M Levy 1, E Maher 1, D Farber 1
PMCID: PMC443188  PMID: 1328299

Abstract

60% of chronic caval dogs with ascites did not respond to atrial natriuretic peptide (ANP) (75 ng.kg-1.min-1) with a natriuresis (TIVC-NR; delta UNaV = 2 +/- 0.8 mu eq/min) whereas the remaining 40% responded normally (TIVC-R; delta UNaV = 216 +/- 50 mu eq/min). Since proximal tubule neutral endopeptidase 24:11 (NEP) destroys most of intrarenal luminal ANP and kinins, we attempted to convert TIVC-NR into TIVC-R by providing NEP inhibition with SQ 28603 at 30 mg/kg. This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC-NR dogs (delta UNaV = 67 +/- 2 mu eq/min) and permitted a natriuresis in the presence of ANP (delta UNaV = 97 +/- 18 mu eq/min). A natriuretic response to ANP could also be induced in TIVC-NR dogs by providing renal arterial bradykinin or intravenous captopril, a kininase inhibitor. Urodilatin, a natriuretic peptide not destroyed by intrarenal NEP was without effect in TIVC-NR dogs but increased UNaV when given to TIVC-R and normal dogs. Providing bradykinin to TIVC-NR now permitted an increment in delta UNaV (62 mu eq/min) when urodilatin was reinfused. TIVC-R dogs could be converted into TIVC-NR by pretreating with a specific bradykinin antagonist before infusing ANP. We conclude that TIVC-NR dogs are deficient in intrarenal kinins but are converted to responding dogs after NEP inhibition because of increased kinin delivery to the inner medullary collecting duct.

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Selected References

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  1. 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]
  2. Brenner B. M., Ballermann B. J., Gunning M. E., Zeidel M. L. Diverse biological actions of atrial natriuretic peptide. Physiol Rev. 1990 Jul;70(3):665–699. doi: 10.1152/physrev.1990.70.3.665. [DOI] [PubMed] [Google Scholar]
  3. Figueroa C. D., Lewis H. M., MacIver A. G., Mackenzie J. C., Bhoola K. D. Cellular localisation of atrial natriuretic factor in the human kidney. Nephrol Dial Transplant. 1990;5(1):25–31. doi: 10.1093/ndt/5.1.25. [DOI] [PubMed] [Google Scholar]
  4. Gerbes A. L., Kollenda M. C., Vollmar A. M., Reichen J., Vakil N., Scarborough R. M. Altered density of glomerular binding sites for atrial natriuretic factor in bile duct-ligated rats with ascites. Hepatology. 1991 Mar;13(3):562–566. [PubMed] [Google Scholar]
  5. Goetz K. L. Renal natriuretic peptide (urodilatin?) and atriopeptin: evolving concepts. Am J Physiol. 1991 Dec;261(6 Pt 2):F921–F932. doi: 10.1152/ajprenal.1991.261.6.F921. [DOI] [PubMed] [Google Scholar]
  6. Levy M. Comparative effects of diuretics and atrial peptide in chronic caval dogs. Am J Physiol. 1990 Apr;258(4 Pt 2):F768–F774. doi: 10.1152/ajprenal.1990.258.4.F768. [DOI] [PubMed] [Google Scholar]
  7. Levy M. Effects of acute volume expansion and altered hemodynamics on renal tubular function in chronic caval dogs. J Clin Invest. 1972 Apr;51(4):922–938. doi: 10.1172/JCI106887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. López C., Jiménez W., Arroyo V., La Villa G., Gaya J., Clària J., Rivera F., Rodés J. Role of altered systemic hemodynamics in the blunted renal response to atrial natriuretic peptide in rats with cirrhosis and ascites. J Hepatol. 1989 Sep;9(2):217–226. doi: 10.1016/0168-8278(89)90054-8. [DOI] [PubMed] [Google Scholar]
  9. Maher E., Cernacek P., Levy M. Heterogeneous renal responses to atrial natriuretic factor. I. Chronic caval dogs. Am J Physiol. 1989 Nov;257(5 Pt 2):R1057–R1067. doi: 10.1152/ajpregu.1989.257.5.R1057. [DOI] [PubMed] [Google Scholar]
  10. Maher E., Cernacek P., Levy M. Heterogeneous renal responses to atrial natriuretic factor. II. Cirrhotic dogs. Am J Physiol. 1989 Nov;257(5 Pt 2):R1068–R1074. doi: 10.1152/ajpregu.1989.257.5.R1068. [DOI] [PubMed] [Google Scholar]
  11. Maher E., Cernacek P., Levy M. Physiological features of edematous dogs unresponsive to atrial natriuretic peptide. Am J Physiol. 1990 Jun;258(6 Pt 2):F1490–F1496. doi: 10.1152/ajprenal.1990.258.6.F1490. [DOI] [PubMed] [Google Scholar]
  12. Maher E., Cernacek P., Levy M. Serial natriuretic response to atrial peptide in preascitic bile duct ligated dogs. Can J Physiol Pharmacol. 1990 Nov;68(11):1396–1400. doi: 10.1139/y90-212. [DOI] [PubMed] [Google Scholar]
  13. Margulies K. B., Cavero P. G., Seymour A. A., Delaney N. G., Burnett J. C., Jr Neutral endopeptidase inhibition potentiates the renal actions of atrial natriuretic factor. Kidney Int. 1990 Jul;38(1):67–72. doi: 10.1038/ki.1990.168. [DOI] [PubMed] [Google Scholar]
  14. Margulies K. B., Perrella M. A., McKinley L. J., Burnett J. C., Jr Angiotensin inhibition potentiates the renal responses to neutral endopeptidase inhibition in dogs with congestive heart failure. J Clin Invest. 1991 Nov;88(5):1636–1642. doi: 10.1172/JCI115477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sagnella G. A., Markandu N. D., Buckley M. G., Miller M. A., Singer D. R., Cappuccio F. P., MacGregor G. A. Atrial natriuretic peptides in essential hypertension: basal plasma levels and relationship to sodium balance. Can J Physiol Pharmacol. 1991 Oct;69(10):1592–1600. doi: 10.1139/y91-236. [DOI] [PubMed] [Google Scholar]
  16. Salerno F., Badalamenti S., Incerti P., Capozza L., Mainardi L. Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis. Hepatology. 1988 Jan-Feb;8(1):21–26. doi: 10.1002/hep.1840080106. [DOI] [PubMed] [Google Scholar]
  17. Schulz-Knappe P., Forssmann K., Herbst F., Hock D., Pipkorn R., Forssmann W. G. Isolation and structural analysis of "urodilatin", a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine. Klin Wochenschr. 1988 Sep 1;66(17):752–759. doi: 10.1007/BF01726570. [DOI] [PubMed] [Google Scholar]
  18. Smits G. J., McGraw D. E., Trapani A. J. Interaction of ANP and bradykinin during endopeptidase 24.11 inhibition: renal effects. Am J Physiol. 1990 May;258(5 Pt 2):F1417–F1424. doi: 10.1152/ajprenal.1990.258.5.F1417. [DOI] [PubMed] [Google Scholar]
  19. Sonnenberg H., Honrath U., Wilson D. R. In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF. Am J Physiol. 1990 Aug;259(2 Pt 2):F222–F226. doi: 10.1152/ajprenal.1990.259.2.F222. [DOI] [PubMed] [Google Scholar]
  20. Sybertz E. J., Jr, Chiu P. J., Watkins R. W., Vemulapalli S. Neutral metalloendopeptidase inhibitors as ANF potentiators: sites and mechanisms of action. Can J Physiol Pharmacol. 1991 Oct;69(10):1628–1635. doi: 10.1139/y91-241. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Wilkins M. R., Settle S. L., Stockmann P. T., Needleman P. Maximizing the natriuretic effect of endogenous atriopeptin in a rat model of heart failure. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6465–6469. doi: 10.1073/pnas.87.16.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zeidel M. L., Jabs K., Kikeri D., Silva P. Kinins inhibit conductive Na+ uptake by rabbit inner medullary collecting duct cells. Am J Physiol. 1990 Jun;258(6 Pt 2):F1584–F1591. doi: 10.1152/ajprenal.1990.258.6.F1584. [DOI] [PubMed] [Google Scholar]

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