Rapid Communication

Kidney International (1994) 45, 598–604; doi:10.1038/ki.1994.78

Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells

Hirokazu Tsukahara1, Dmitri V Gordienko1, Burkhard Tonshoff1, Marie C Gelato1 and Micheal S Goligorsky1

1Departments of Medicine, Pediatrics and Physiology and Biophysics, State University of New York at Stony Brook, New York, USA

Correspondence: Michael S Goligorsky MD PhD, Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794-8152, USA.

Received 14 September 1993; Revised 22 October 1993; Accepted 25 October 1993.

Top

Abstract

Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells. Several lines of evidence indicate that insulin-like growth factor-I (IGF-I) is a potent mediator of vasodilation. To elucidate the mechanism and site of action of IGF-I, we performed continuous monitoring of nitric oxide (NO) release from endothelial cells using a highly-sensitive amperometric NO-sensor. Two types of cultured cells were used: human umbilical vein endothelial cells and immortalized rat renal interlobar artery endothelial cells. In separate experiments, [Ca2+]i changes in response to IGF-I were measured spectrofluorometrically in fura-2-loaded cells. Stimulation with IGF-I resulted in a rapid, dose-dependent increase in [NO] as detected by the NO-probe positioned 1 mm above the monolayers, followed by a sustained elevation lasting for at least five minutes. The effect of IGF-I was significantly suppressed by pretreatment with anti-IGF-I antibody, suggesting that it was specific for IGF-I. NG-nitro-L-arginine methyl ester, an inhibitor of NO synthesis, significantly blunted responses to IGF-I, but dexamethasone preincubation did not reduce the IGF-I-induced release of NO. These results indicate that the observed IGF-I-induced release of NO is a result of activation of the constitutive, rather than the inducible type of NO synthase in endothelial cells. Genistein, a tyrosine kinase inhibitor, resulted in a profound suppression of the IGF-I-induced release of NO. IGF-I did not affect [Ca2+]i in either type of cells. Therefore, IGF-I-induced NO production by both types of endothelial cells is mediated via a tyrosine kinase-dependent mechanism. IGF-I may be an important regulator of vascular tone in vivo through NO release from the vascular endothelium, and may contribute to the regulation of renal blood flow under physiological and pathophysiological conditions.

Top

References

  1. Hammerman MR: The growth hormon-insulin-like growth factor axis in kidney. Am J Physiol 257 (Renal Fluid Electrol Physiol 26):F503–F514, 1989 | PubMed | ISI | ChemPort |
  2. Czech MP: Signal transmission by the insulin-like growth factors. Cell 59:235–238, 1989 | Article | PubMed | ISI | ChemPort |
  3. Zumkeller W, Schofield PN: The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney. Virchows Archiv B Cell Pathol 62:207–220, 1992
  4. Guler HP, Eckardt KU, Zapf J, Bauer C, Froesch ER: Insulin-like growth factor I increases glomerular filtration rate and renal plasma flow in man. Acta Endocrinol (Copenh) 121:101–106, 1989 | PubMed | ISI | ChemPort |
  5. Hirschberg R, Kopple JD: Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats. J Clin Invest 83:326–330, 1989 | PubMed | ISI | ChemPort |
  6. Haylor J, Singh I, El Nahas AM: Nitric oxide synthesis inhibitor prevents vasodilation by insulin-like growth factor I. Kidney Int 39:333–335, 1991
  7. Baumann U, Eisenhauer T, Hartmann H: Increase of glomerular filtration rate and renal plasma flow by insulin-like growth factor-I during euglycaemic clamping in anaesthetized rats. Eur J Clin Invest 22:204–209, 1992
  8. Bar RS, Boes M, Yorek M: Processing of insulin-like growth factors I and II by capillary and large vessel endothelial cells. Endocrinology 118:1072–1080, 1986
  9. Bar RS, Boes M, Dake BL, Booth BA, Henley SA, Sandra A: Insulin, insulin-like growth factors, and vascular endothelium. Am J Med 85(Suppl 5A):59–70, 1988
  10. Conti FG, Elliot SJ, Striker LJ, Striker GE: Binding of insulin-like growth factor-I by glomerular endothelial and epithelial cells: Further evidence for IGF-I action in the renal glomerulus. Biochem Biophys Res Commun 163:952–958, 1989 | PubMed |
  11. Palmer RMJ, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (Lond) 327:524–526, 1987 | Article | PubMed | ISI | ChemPort |
  12. Palmer RMJ, Ashton DS, Moncada S: Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature (Lond) 333:664–666, 1988 | Article | PubMed | ISI | ChemPort |
  13. Schmidt HHHW, Pollock JS, Nakane M, Förstermann U, Murad F: Ca2+/calmodulin-regulated nitric oxide synthases. Cell Calcium 13:427–434, 1992 | Article | PubMed | ChemPort |
  14. Sessa WC, Harrison JK, Barber CM, Zeng D, Durieux ME, D'Angelo DD, Lynch KR, Peach MJ: Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide synthase. J Biol Chem 267:15274–15276, 1992 | PubMed | ChemPort |
  15. Marsden PA, Goligorsky MS, Brenner BM: Endothelial cell biology in relation to current concepts of vessel wall structure and function. J Am Soc Nephrol 1:931–948, 1991 | PubMed | ISI | ChemPort |
  16. Tsukahara H, Gordienko DV, Goligorsky MS: Continuous monitoring of nitric oxide release from human umbilical vein endothelial cells. Biochem Biophys Res Commun 193:722–729, 1993 | Article | PubMed | ISI | ChemPort |
  17. Jaffe EA: Culture of human endothelial cells. Transplant Proc 12(Suppl 1):49–53, 1980
  18. Loeber G, Tevethia MJ, Schwedes JF, Tegtmeyer P: Temperature-sensitive mutants identify crucial structural regions of simian virus 40 large T antigen. J Virol 63:4426–4430, 1989 | PubMed | ISI | ChemPort |
  19. Shibuki K: An electrochemical microprobe for detecting nitric oxide release in brain tissue. Neurosci Res 9:69–76, 1990 | Article | PubMed | ChemPort |
  20. Shibuki K, Okada D: Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature (Lond) 349:326–328, 1991 | Article | PubMed | ISI | ChemPort |
  21. Iijima K, Lin L, Nasjletti A, Goligorsky MS: Intracellular ramification of endothelin signal. Am J Physiol 260 (Cell Physiol 29) C982–C992, 1991
  22. Bahou WF, Ginsburg D, Sikkink R, Litwiller R, Fass DN: A monoclonal antibody to von Willebrand factor (vWF) inhibits factor VIII binding: Localization of its antigenic determinant to a non-adecapeptide at the amino terminus of the mature vWF polypeptide. J Clin Invest 84:56–61, 1989
  23. Radomski MW, Palmer RMJ, Moncada S: Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047, 1990 | PubMed | ChemPort |
  24. MacKay K, Striker LJ, Elliot S, Pinkert CA, Brinster RL, Striker GE: Glomerular epithelial, mesangial, and endothelial cell lines from transgenic mice. Kidney Int 33:677–687, 1988 | PubMed | ISI | ChemPort |
  25. Laulajainen T, Julkunen I, Haltia A, Knuutila S, Miettinen A, Holthöfer H: Establishment and characterization of a rat glomerular endothelial cell line. Lab Invest 69:183–192, 1993 | PubMed |
  26. Catanese VM, Sciavolino PJ, Lango MN: Discordant, organ-specific regulation of insulin-like growth factor-I messenger ribonucleic acid in insulin-deficient diabetes in rats. Endocrinology 132:496–503, 1993
  27. Flyvbjerg A, Thorlacius-Ussing O, Næraa R, Ingerslev J, Ørskov H: Kidney tissue somatomedin C and initial renal growth in diabetic and uninephrectomised rats. Diabetologia 31:310–314, 1988 | PubMed | ISI | ChemPort |
  28. Bank N, Aynedjian HS: Role of EDRF (nitric oxide) in diabetic renal hyperfiltration. Kidney Int 43:1306–1312, 1993 | PubMed | ISI | ChemPort |
  29. Christiansen JS, Gammelgaard J, Frandsen M, Parving HH: Increased kidney size, glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics. Diabetologia 20:451–456, 1981 | PubMed | ISI | ChemPort |
  30. Mogensen CE: Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Invest 46:201–206, 1986 | PubMed | ISI | ChemPort |
  31. Merimee TJ, Zapf J, Froesch ER: Insulin-like growth factors: Studies in diabetics with and without retinopathy. N Engl J Med 309:527–530, 1983 | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT