Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Sep;80(3):698–705. doi: 10.1172/JCI113124

In vitro and in vivo protective effect of atriopeptin III on ischemic acute renal failure.

M Nakamoto, J I Shapiro, P F Shanley, L Chan, R W Schrier
PMCID: PMC442293  PMID: 2957391

Abstract

The effect of atriopeptin III (AP-III) on ameliorate ischemic acute renal failure was first examined in the isolated perfused kidney. Isolated rat kidneys were clamped for 1 h and reperfused for 30 min without therapy and then perfused with either 0 (control) or 100 micrograms/dl AP-III. In this system AP-III significantly improved renal plasma flow (39.6 +/- 2.4 vs. 32.2 +/- 2.1 ml/min per g; P less than 0.05) inulin clearance (182.6 +/- 49.2 vs. 24.6 +/- 6.2 microliters/min per g; P less than 0.05), urine flow (52.9 +/- 12.1 vs. 7.1 +/- 0.8 microliters/min per g, P less than 0.01), and net tubular sodium reabsorption (21.2 +/- 6.6 vs. 2.9 +/- 0.9 mumol/min per g, P less than 0.05) as compared with control. A second series of in vivo studies experiments were performed using 1 h of bilateral renal artery clamping followed by an intravenous infusion of either saline alone (control) or AP-III (0.20 microgram/kg per min) for 60 min. The results demonstrated that inulin clearance (244.4 +/- 25.1 vs. 15.8 +/- 8.2 microliters/min per 100 g; P less than 0.01), urine flow (23.1 +/- 5.9 vs. 1.1 +/- 0.5 microliters/min per 100 g; P less than 0.01), and net tubular sodium reabsorption (38.9 +/- 4.7 vs. 4.3 +/- 1.6 mumol/min per 100 g; P less than 0.01) were significantly higher in AP-III-treated rats than controls during the hour of AP-III infusion. In 1 h posttreatment study this significant protective effect of AP-III was documented to persist. In more chronic studies animals treated acutely with AP-III had lower serum creatinine concentration at 24 h (1.8 +/- 0.3 vs. 3.3 +/- 0.4 mg/dl; P less than 0.01) and 48 (1.0 +/- 0.2 vs. 2.4 +/- 4.0 mg/dl; P less than 0.01) after the 60 min of ischemia than controls. Renal adenosine triphosphate regeneration as assessed by P-31 nuclear magnetic resonance during reflow was also significantly improved in AP-III-treated animals at 1 h (3.03 +/- 0.30 vs. 1.45 +/- 0.40 mumol/g dry wt; P less than 0.05) and 2 h (3.98 +/- 0.46 vs. 1.80 +/- 0.05 mumol/g dry wt; P less than 0.01) or reflow as compared with control rats. Thus, AP-III significantly ameliorates ischemic acute renal failure both in vitro and in vivo in the rat.

Full text

PDF
698

Images in this article

701Image
on p.701
701Image
on p.701
701Image
on p.701

Selected References

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

  1. Balaban R. S., Gadian D. G., Radda G. K. Phosphorus nuclear magnetic resonance study of the rat kidney in vivo. Kidney Int. 1981 Nov;20(5):575–579. doi: 10.1038/ki.1981.179. [DOI] [PubMed] [Google Scholar]
  2. Ballermann B. J., Hoover R. L., Karnovsky M. J., Brenner B. M. Physiologic regulation of atrial natriuretic peptide receptors in rat renal glomeruli. J Clin Invest. 1985 Dec;76(6):2049–2056. doi: 10.1172/JCI112207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burke T. J., Arnold P. E., Gordon J. A., Bulger R. E., Dobyan D. C., Schrier R. W. Protective effect of intrarenal calcium membrane blockers before or after renal ischemia. Functional, morphological, and mitochondrial studies. J Clin Invest. 1984 Nov;74(5):1830–1841. doi: 10.1172/JCI111602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burke T. J., Arnold P. E., Schrier R. W. Prevention of ischemic acute renal failure with impermeant solutes. Am J Physiol. 1983 Jun;244(6):F646–F649. doi: 10.1152/ajprenal.1983.244.6.F646. [DOI] [PubMed] [Google Scholar]
  5. Burke T. J., Cronin R. E., Duchin K. L., Peterson L. N., Schrier R. W. Ischemia and tubule obstruction during acute renal failure in dogs: mannitol in protection. Am J Physiol. 1980 Apr;238(4):F305–F314. doi: 10.1152/ajprenal.1980.238.4.F305. [DOI] [PubMed] [Google Scholar]
  6. Conger J. D., Robinette J. B., Guggenheim S. J. Effect of acetylcholine on the early phase of reversible norepinephrine-induced acute renal failure. Kidney Int. 1981 Mar;19(3):399–409. doi: 10.1038/ki.1981.32. [DOI] [PubMed] [Google Scholar]
  7. Epstein F. H., Brosnan J. T., Tange J. D., Ross B. D. Improved function with amino acids in the isolated perfused kidney. Am J Physiol. 1982 Sep;243(3):F284–F292. doi: 10.1152/ajprenal.1982.243.3.F284. [DOI] [PubMed] [Google Scholar]
  8. Freeman D. M., Chan L., Yahaya H., Holloway P., Ross B. D. Magnetic resonance spectroscopy for the determination of renal metabolic rate in vivo. Kidney Int. 1986 Jul;30(1):35–42. doi: 10.1038/ki.1986.147. [DOI] [PubMed] [Google Scholar]
  9. Gorfinkel H. J., Szidon J. P., Hirsch L. J., Fishman A. P. Renal performance in experimental cardiogenic shock. Am J Physiol. 1972 May;222(5):1260–1268. doi: 10.1152/ajplegacy.1972.222.5.1260. [DOI] [PubMed] [Google Scholar]
  10. Hanley M. J. Isolated nephron segments in a rabbit model of ischemic acute renal failure. Am J Physiol. 1980 Jul;239(1):F17–F23. doi: 10.1152/ajprenal.1980.239.1.F17. [DOI] [PubMed] [Google Scholar]
  11. Heidbreder E., Schafferhans K., Schramm D., Götz R., Heidland A. Toxic renal failure in the rat: beneficial effects of atrial natriuretic factor. Klin Wochenschr. 1986;64 (Suppl 6):78–82. [PubMed] [Google Scholar]
  12. Huang C. L., Lewicki J., Johnson L. K., Cogan M. G. Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest. 1985 Feb;75(2):769–773. doi: 10.1172/JCI111759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levinsky N. G. Pathophysiology of acute renal failure. N Engl J Med. 1977 Jun 23;296(25):1453–1458. doi: 10.1056/NEJM197706232962509. [DOI] [PubMed] [Google Scholar]
  14. Nishiitsutsuji-Uwo J. M., Ross B. D., Krebs H. A. Metabolic activities of the isolated perfused rat kidney. Biochem J. 1967 Jun;103(3):852–862. doi: 10.1042/bj1030852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Patak R. V., Fadem S. Z., Lifschitz M. D., Stein J. H. Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog. Kidney Int. 1979 Mar;15(3):227–237. doi: 10.1038/ki.1979.30. [DOI] [PubMed] [Google Scholar]
  16. Ross B. D., Epstein F. H., Leaf A. Sodium reabsorption in the perfused rat kidney. Am J Physiol. 1973 Nov;225(5):1165–1171. doi: 10.1152/ajplegacy.1973.225.5.1165. [DOI] [PubMed] [Google Scholar]
  17. Schafferhans K., Heidbreder E., Grimm D., Heidland A. Norepinephrine-induced acute renal failure: beneficial effects of atrial natriuretic factor. Nephron. 1986;44(3):240–244. doi: 10.1159/000183994. [DOI] [PubMed] [Google Scholar]
  18. Sehr P. A., Bore P. J., Papatheofanis J., Radda G. K. Non-destructive measurement of metabolites and tissue pH in the kidney by 31P nuclear magnetic resonance. Br J Exp Pathol. 1979 Dec;60(6):632–641. [PMC free article] [PubMed] [Google Scholar]
  19. Shanley P. F., Rosen M. D., Brezis M., Silva P., Epstein F. H., Rosen S. Topography of focal proximal tubular necrosis after ischemia with reflow in the rat kidney. Am J Pathol. 1986 Mar;122(3):462–468. [PMC free article] [PubMed] [Google Scholar]
  20. Shapiro J. I., Cheung C., Itabashi A., Chan L., Schrier R. W. The effect of verapamil on renal function after warm and cold ischemia in the isolated perfused rat kidney. Transplantation. 1985 Dec;40(6):596–600. doi: 10.1097/00007890-198512000-00004. [DOI] [PubMed] [Google Scholar]
  21. Shenker Y., Sider R. S., Ostafin E. A., Grekin R. J. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema. J Clin Invest. 1985 Oct;76(4):1684–1687. doi: 10.1172/JCI112154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Siegel N. J., Avison M. J., Reilly H. F., Alger J. R., Shulman R. G. Enhanced recovery of renal ATP with postischemic infusion of ATP-MgCl2 determined by 31P-NMR. Am J Physiol. 1983 Oct;245(4):F530–F534. doi: 10.1152/ajprenal.1983.245.4.F530. [DOI] [PubMed] [Google Scholar]
  23. Sonnenberg H., Honrath U., Chong C. K., Wilson D. R. Atrial natriuretic factor inhibits sodium transport in medullary collecting duct. Am J Physiol. 1986 Jun;250(6 Pt 2):F963–F966. doi: 10.1152/ajprenal.1986.250.6.F963. [DOI] [PubMed] [Google Scholar]
  24. Tanner G. A., Sloan K. L., Sophasan S. Effects of renal artery occlusion on kidney function in the rat. Kidney Int. 1973 Dec;4(6):377–389. doi: 10.1038/ki.1973.134. [DOI] [PubMed] [Google Scholar]
  25. Venkatachalam M. A., Bernard D. B., Donohoe J. F., Levinsky N. G. Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments. Kidney Int. 1978 Jul;14(1):31–49. doi: 10.1038/ki.1978.87. [DOI] [PubMed] [Google Scholar]
  26. WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
  27. Wakitani K., Cole B. R., Geller D. M., Currie M. G., Adams S. P., Fok K. F., Needleman P. Atriopeptins: correlation between renal vasodilation and natriuresis. Am J Physiol. 1985 Jul;249(1 Pt 2):F49–F53. doi: 10.1152/ajprenal.1985.249.1.F49. [DOI] [PubMed] [Google Scholar]
  28. Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
  29. Wilson D. R., Arnold P. E., Burke T. J., Schrier R. W. Mitochondrial calcium accumulation and respiration in ischemic acute renal failure in the rat. Kidney Int. 1984 Mar;25(3):519–526. doi: 10.1038/ki.1984.48. [DOI] [PubMed] [Google Scholar]

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

RESOURCES