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. 1987 Sep;80(3):670–674. doi: 10.1172/JCI113120

Elevated plasma atrial natriuretic peptide levels in diabetic rats. Potential mediator of hyperfiltration.

F V Ortola, B J Ballermann, S Anderson, R E Mendez, B M Brenner
PMCID: PMC442289  PMID: 2957390

Abstract

Infusion of atrial natriuretic peptide (ANP) increases the glomerular filtration rate (GFR), and ANP is released from cardiac myocytes in response to extracellular fluid volume expansion. Since diabetes mellitus is associated with glomerular hyperfiltration and volume expansion, we investigated the relationship between ANP and GFR in diabetic rats given insulin to achieve stable moderate hyperglycemia or normoglycemia. At 2 wk after induction of diabetes, moderately hyperglycemic diabetic rats exhibited elevations of plasma ANP levels averaging 281 +/- 28 pg/ml vs. 158 +/- 15 pg/ml in normoglycemic diabetic rats. In hyperglycemic rats, the GFR was also elevated on average to 2.24 +/- 0.28 ml/min as compared with 1.71 +/- 0.13 ml/min in normoglycemic diabetic rats. To test further the relationship between ANP and GFR in diabetes, moderately hyperglycemic diabetic rats were infused either with a specific ANP antiserum or with nonimmune serum. The infusion of specific ANP antiserum uniformly reduced the GFR on average from 2.38 +/- 0.1 ml/min to 1.60 +/- 0.1 ml/min, whereas the infusion of nonimmune serum was without effect. It is concluded that elevated endogenous ANP levels contribute to the hyperfiltration observed in early diabetes in the rat.

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Selected References

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

  1. Ballermann B. J., Bloch K. D., Seidman J. G., Brenner B. M. Atrial natriuretic peptide transcription, secretion, and glomerular receptor activity during mineralocorticoid escape in the rat. J Clin Invest. 1986 Sep;78(3):840–843. doi: 10.1172/JCI112650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beasley D., Malvin R. L. Atrial extracts increase glomerular filtration rate in vivo. Am J Physiol. 1985 Jan;248(1 Pt 2):F24–F30. doi: 10.1152/ajprenal.1985.248.1.F24. [DOI] [PubMed] [Google Scholar]
  3. Brenner B. M. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985 Sep;249(3 Pt 2):F324–F337. doi: 10.1152/ajprenal.1985.249.3.F324. [DOI] [PubMed] [Google Scholar]
  4. Bröchner-Mortensen J. Glomerular filtration rate and extracellular fluid volumes during normoglycemia and moderate hyperglycemia in diabetics. Scand J Clin Lab Invest. 1973 Dec;32(4):311–316. doi: 10.3109/00365517309084353. [DOI] [PubMed] [Google Scholar]
  5. Burnett J. C., Jr, Granger J. P., Opgenorth T. J. Effects of synthetic atrial natriuretic factor on renal function and renin release. Am J Physiol. 1984 Nov;247(5 Pt 2):F863–F866. doi: 10.1152/ajprenal.1984.247.5.F863. [DOI] [PubMed] [Google Scholar]
  6. Christiansen J. S., Frandsen M., Parving H. H. The effect of intravenous insulin infusion on kidney function in insulin-dependent diabetes mellitus. Diabetologia. 1981 Mar;20(3):199–204. doi: 10.1007/BF00252628. [DOI] [PubMed] [Google Scholar]
  7. Christiansen J. S., Gammelgaard J., Frandsen M., Parving H. H. Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia. 1981 Apr;20(4):451–456. doi: 10.1007/BF00253406. [DOI] [PubMed] [Google Scholar]
  8. Christiansen J. S., Gammelgaard J., Tronier B., Svendsen P. A., Parving H. H. Kidney function and size in diabetics before and during initial insulin treatment. Kidney Int. 1982 May;21(5):683–688. doi: 10.1038/ki.1982.81. [DOI] [PubMed] [Google Scholar]
  9. Christlieb A. R. Renin, angiotensin, and norepinephrine in alloxan diabetes. Diabetes. 1974 Dec;23(12):962–970. doi: 10.2337/diab.23.12.962. [DOI] [PubMed] [Google Scholar]
  10. Ditzel J., Junker K. Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics. Br Med J. 1972 Apr 1;2(5804):13–19. doi: 10.1136/bmj.2.5804.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ditzel J., Schwartz M. Abnormally increased glomerular filtration rate in short-term insulin-treated diabetic subjects. Diabetes. 1967 Apr;16(4):264–267. doi: 10.2337/diab.16.4.264. [DOI] [PubMed] [Google Scholar]
  12. Dunn B. R., Ichikawa I., Pfeffer J. M., Troy J. L., Brenner B. M. Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat. Circ Res. 1986 Sep;59(3):237–246. doi: 10.1161/01.res.59.3.237. [DOI] [PubMed] [Google Scholar]
  13. FUHR J., KACZMARCZYK J., KRUTTGEN C. D. Eine einfache colorimetrische Methode zur Inulinbestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin Wochenschr. 1955 Aug 1;33(29-30):729–730. doi: 10.1007/BF01473295. [DOI] [PubMed] [Google Scholar]
  14. Garlick R. L., Mazer J. S., Higgins P. J., Bunn H. F. Characterization of glycosylated hemoglobins. Relevance to monitoring of diabetic control and analysis of other proteins. J Clin Invest. 1983 May;71(5):1062–1072. doi: 10.1172/JCI110856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hostetter T. H., Rennke H. G., Brenner B. M. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. doi: 10.1016/0002-9343(82)90490-9. [DOI] [PubMed] [Google Scholar]
  16. Hostetter T. H., Troy J. L., Brenner B. M. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. doi: 10.1038/ki.1981.33. [DOI] [PubMed] [Google Scholar]
  17. Lang R. E., Thölken H., Ganten D., Luft F. C., Ruskoaho H., Unger T. Atrial natriuretic factor--a circulating hormone stimulated by volume loading. Nature. 1985 Mar 21;314(6008):264–266. doi: 10.1038/314264a0. [DOI] [PubMed] [Google Scholar]
  18. Maddox D. A., Price D. C., Rector F. C., Jr Effects of surgery on plasma volume and salt and water excretion in rats. Am J Physiol. 1977 Dec;233(6):F600–F606. doi: 10.1152/ajprenal.1977.233.6.F600. [DOI] [PubMed] [Google Scholar]
  19. Mogensen C. E., Andersen M. J. Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes. 1973 Sep;22(9):706–712. doi: 10.2337/diab.22.9.706. [DOI] [PubMed] [Google Scholar]
  20. Mogensen C. E., Andersen M. J. Increased kidney size and glomerular filtration rate in untreated juvenile diabetes: normalization by insulin-treatment. Diabetologia. 1975 Jun;11(3):221–224. doi: 10.1007/BF00422325. [DOI] [PubMed] [Google Scholar]
  21. Mogensen C. E., Christensen C. K. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984 Jul 12;311(2):89–93. doi: 10.1056/NEJM198407123110204. [DOI] [PubMed] [Google Scholar]
  22. Mogensen C. E. Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest. 1971 Sep;28(1):91–100. doi: 10.3109/00365517109090667. [DOI] [PubMed] [Google Scholar]
  23. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tanaka I., Misono K. S., Inagami T. Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay. Biochem Biophys Res Commun. 1984 Oct 30;124(2):663–668. doi: 10.1016/0006-291x(84)91606-1. [DOI] [PubMed] [Google Scholar]
  25. Vari R. C., Freeman R. H., Davis J. O., Villarreal D., Verburg K. M. Effect of synthetic atrial natriuretic factor on aldosterone secretion in the rat. Am J Physiol. 1986 Jul;251(1 Pt 2):R48–R52. doi: 10.1152/ajpregu.1986.251.1.R48. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wiseman M. J., Saunders A. J., Keen H., Viberti G. Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes. N Engl J Med. 1985 Mar 7;312(10):617–621. doi: 10.1056/NEJM198503073121004. [DOI] [PubMed] [Google Scholar]
  28. Zatz R., Dunn B. R., Meyer T. W., Anderson S., Rennke H. G., Brenner B. M. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986 Jun;77(6):1925–1930. doi: 10.1172/JCI112521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. deLeiva A., Christlieb A. R., Melby J. C., Graham C. A., Day R. P., Luetscher J. A., Zager P. G. Big renin and biosynthetic defect of aldosterone in diabetes mellitus. N Engl J Med. 1976 Sep 16;295(12):639–643. doi: 10.1056/NEJM197609162951203. [DOI] [PubMed] [Google Scholar]

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