Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 May 14;93(10):4957–4961. doi: 10.1073/pnas.93.10.4957

Hemodynamic effects of epidermal growth factor in conscious rats and monkeys.

J A Keiser 1, M J Ryan 1
PMCID: PMC39387  PMID: 8643511

Abstract

The therapeutic application of growth factors to human disease has become closer to reality with the advent of faster means of synthesizing these molecules and novel drug delivery strategies. Epidermal growth factor (EGF) belongs to a large family of molecules with the ability to modulate growth. Purified extracts of EGF have been used clinically to modulate gastrointestinal secretion of hormones and accelerate healing. EGF is also reported to have both vascular smooth muscle contractile and relaxing activity Cardiovascular studies were performed with the bioactive 48-amino acid fragment of human EGF in rodents and primates to determine the effects of EGF on blood pressure and heart rate in conscious animals. Intravenous infusion of EGF induced an initial pressor response in rats followed by a prolonged decrease in blood pressure. In contrast, in monkeys, EGF had dose-related blood pressure-lowering effects only; significant hypotension was observed at doses ranging from 3 to 300 microg/kg i.v. Hypotension was associated with modest tachycardia in both species. To our knowledge, this is the first report of hemodynamic effects of EGF in primates, and it clearly documents that the mitogenic role of growth factors such as EGF is but one aspect of their physiology.

Full text

PDF
4957

Selected References

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

  1. Antonipillai I. Epidermal growth factor is a potent inhibitor of renin secretion. Hypertension. 1993 May;21(5):654–659. doi: 10.1161/01.hyp.21.5.654. [DOI] [PubMed] [Google Scholar]
  2. Berk B. C., Alexander R. W. Vasoactive effects of growth factors. Biochem Pharmacol. 1989 Jan 15;38(2):219–225. doi: 10.1016/0006-2952(89)90030-0. [DOI] [PubMed] [Google Scholar]
  3. Berk B. C., Brock T. A., Webb R. C., Taubman M. B., Atkinson W. J., Gimbrone M. A., Jr, Alexander R. W. Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction. J Clin Invest. 1985 Mar;75(3):1083–1086. doi: 10.1172/JCI111772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burgess A. W., Lloyd C. J., Smith S., Stanley E., Walker F., Fabri L., Simpson R. J., Nice E. C. Murine epidermal growth factor: structure and function. Biochemistry. 1988 Jul 12;27(14):4977–4985. doi: 10.1021/bi00414a005. [DOI] [PubMed] [Google Scholar]
  5. Carter N. B., Fawcett A. A., Hales J. R., Moore G. P., Panaretto B. A. Circulatory effects of a depilatory dose of mouse epidermal growth factor in sheep. J Physiol. 1988 Sep;403:27–39. doi: 10.1113/jphysiol.1988.sp017236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casscells W. Growth factor therapies for vascular injury and ischemia. Circulation. 1995 Jun 1;91(11):2699–2702. doi: 10.1161/01.cir.91.11.2699. [DOI] [PubMed] [Google Scholar]
  7. Cohen S., Carpenter G., Lembach K. J. Interaction of epidermal growth factor (EGF) with cultured fibroblasts. Adv Metab Disord. 1975;8:265–284. doi: 10.1016/b978-0-12-027308-9.50024-x. [DOI] [PubMed] [Google Scholar]
  8. De Marco A., Mayo K. H., Bartolotti F., Scalia S., Menegatti E., Kaptein R. Proton NMR and photochemically induced dynamic nuclear polarization studies of peptide fragments obtained by controlled proteolysis of mouse epidermal growth factor. J Biol Chem. 1986 Oct 15;261(29):13510–13516. [PubMed] [Google Scholar]
  9. Elder J. B., Ganguli P. C., Gillespie I. E., Gerring E. L., Gregory H. Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects. Gut. 1975 Nov;16(11):887–893. doi: 10.1136/gut.16.11.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Elder J. B., Gillespie I. E., Ganguli P. C., Delamore W. I., Gregory H. Effect of urogastrone in the Zollinger-Ellison syndrome. Lancet. 1975 Sep 6;2(7932):424–427. doi: 10.1016/s0140-6736(75)90842-9. [DOI] [PubMed] [Google Scholar]
  11. Gan B. S., Bolt G. R., Hollenberg M. D., MacCannell K. L. Species variation in the vascular effects of epidermal growth factor-urogastrone. Proc West Pharmacol Soc. 1986;29:483–484. [PubMed] [Google Scholar]
  12. Gan B. S., MacCannell K. L., Hollenberg M. D. Epidermal growth factor-urogastrone causes vasodilatation in the anesthetized dog. J Clin Invest. 1987 Jul;80(1):199–206. doi: 10.1172/JCI113048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gow C. B., Wilkinson M., Silvapulle M. J., Moore G. P. Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor. J Endocrinol. 1992 Oct;135(1):91–101. doi: 10.1677/joe.0.1350091. [DOI] [PubMed] [Google Scholar]
  14. Guglietta A., Lesch C. A. Effect of h-EGF and h-EGF 1-48 on histamine-stimulated gastric acid secretion in rats and monkeys. J Physiol Paris. 1993;87(6):343–347. [PubMed] [Google Scholar]
  15. Humes H. D., Cieslinski D. A., Coimbra T. M., Messana J. M., Galvao C. Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure. J Clin Invest. 1989 Dec;84(6):1757–1761. doi: 10.1172/JCI114359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Imada O., Hayashi N., Masamoto K., Kasuga S., Fuwa T., Nakagawa S. Long-latency growth-promoting activity of EGF when administered to mice at the neonatal stage. Am J Physiol. 1987 Sep;253(3 Pt 1):E251–E254. doi: 10.1152/ajpendo.1987.253.3.E251. [DOI] [PubMed] [Google Scholar]
  17. Isner J. M., Walsh K., Symes J., Pieczek A., Takeshita S., Lowry J., Rossow S., Rosenfield K., Weir L., Brogi E. Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease. Circulation. 1995 Jun 1;91(11):2687–2692. doi: 10.1161/01.cir.91.11.2687. [DOI] [PubMed] [Google Scholar]
  18. Itoh M., Matsuo Y. Gastric ulcer treatment with intravenous human epidermal growth factor: a double-blind controlled clinical study. J Gastroenterol Hepatol. 1994;9 (Suppl 1):S78–S83. doi: 10.1111/j.1440-1746.1994.tb01307.x. [DOI] [PubMed] [Google Scholar]
  19. Kawaida K., Matsumoto K., Shimazu H., Nakamura T. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4357–4361. doi: 10.1073/pnas.91.10.4357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Killion D., Canfield C., Norman J., Rosenthal J. T. Exogenous epidermal growth factor fails to accelerate functional recovery in the autotransplanted ischemic pig kidney. J Urol. 1993 Nov;150(5 Pt 1):1551–1556. doi: 10.1016/s0022-5347(17)35840-8. [DOI] [PubMed] [Google Scholar]
  21. Koffman C. G., Elder J. B., Ganguli P. C., Gregory H., Geary C. G. Effect of urogastrone on gastric secretion and serum gastrin concentration in patients with duodenal ulceration. Gut. 1982 Nov;23(11):951–956. doi: 10.1136/gut.23.11.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Konturek S. J., Dembinski A., Warzecha Z., Brzozowski T., Gregory H. Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology. 1988 Jun;94(6):1300–1307. doi: 10.1016/0016-5085(88)90667-1. [DOI] [PubMed] [Google Scholar]
  23. Laniyonu A. A., Saifeddine M., Yang S. G., Hollenberg M. D. Tyrosine kinase inhibitors and the contractile action of G-protein-linked vascular agonists. Can J Physiol Pharmacol. 1994 Sep;72(9):1075–1085. doi: 10.1139/y94-150. [DOI] [PubMed] [Google Scholar]
  24. Maraschin R., Bussi R., Conz A., Orlando L., Pirovano R., Nyska A. Toxicological evaluation of u-hEGF. Toxicol Pathol. 1995 May-Jun;23(3):356–366. doi: 10.1177/019262339502300312. [DOI] [PubMed] [Google Scholar]
  25. Miller S. B., Martin D. R., Kissane J., Hammerman M. R. Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats. Am J Physiol. 1994 Jan;266(1 Pt 2):F129–F134. doi: 10.1152/ajprenal.1994.266.1.F129. [DOI] [PubMed] [Google Scholar]
  26. Moore G. P., Wilkinson M., Panaretto B. A., Delbridge L. W., Posen S. Epidermal growth factor causes hypocalcemia in sheep. Endocrinology. 1986 Apr;118(4):1525–1529. doi: 10.1210/endo-118-4-1525. [DOI] [PubMed] [Google Scholar]
  27. Morin N. J., Laurent G., Nonclercq D., Toubeau G., Heuson-Stiennon J. A., Bergeron M. G., Beauchamp D. Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats. Am J Physiol. 1992 Nov;263(5 Pt 2):F806–F811. doi: 10.1152/ajprenal.1992.263.5.F806. [DOI] [PubMed] [Google Scholar]
  28. Muramatsu I., Hollenberg M. D., Lederis K. Modulation by epidermal growth factor--urogastrone of contraction in isolated canine helical mesenteric arterial strips. Can J Physiol Pharmacol. 1986 Dec;64(12):1561–1565. doi: 10.1139/y86-262. [DOI] [PubMed] [Google Scholar]
  29. Muramatsu I., Hollenberg M. D., Lederis K. Vascular actions of epidermal growth factor-urogastrone: possible relationship to prostaglandin production. Can J Physiol Pharmacol. 1985 Aug;63(8):994–999. doi: 10.1139/y85-164. [DOI] [PubMed] [Google Scholar]
  30. Mustoe T. A., Pierce G. F., Morishima C., Deuel T. F. Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest. 1991 Feb;87(2):694–703. doi: 10.1172/JCI115048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Namiki A., Akatsuka N. Vascular smooth muscle relaxation induced by epidermal growth factor is endothelium-dependent. Eur J Pharmacol. 1990 May 16;180(2-3):247–254. doi: 10.1016/0014-2999(90)90308-s. [DOI] [PubMed] [Google Scholar]
  32. Saifeddine M., Laniyonu A., Ahmad S., Hollenberg M. D. Bi-directional control of smooth muscle tension: regulation by tyrosine kinase and tyrosine phosphatase. Proc West Pharmacol Soc. 1994;37:21–24. [PubMed] [Google Scholar]
  33. Tashjian A. H., Jr, Voelkel E. F., Lloyd W., Derynck R., Winkler M. E., Levine L. Actions of growth factors on plasma calcium. Epidermal growth factor and human transforming growth factor-alpha cause elevation of plasma calcium in mice. J Clin Invest. 1986 Nov;78(5):1405–1409. doi: 10.1172/JCI112728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Weinberg J. M., Nissim I., Roeser N. F., Davis J. A., Schultz S., Nissim I. Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules. Am J Physiol. 1991 Mar;260(3 Pt 2):F410–F419. doi: 10.1152/ajprenal.1991.260.3.F410. [DOI] [PubMed] [Google Scholar]
  35. Yang S. G., Ahmad S., Wong N. C., Hollenberg M. D. Ligand binding characterization and molecular analysis of distinct epidermal growth factor-urogastrone receptors in cultured smooth muscle and epithelial cells from guinea pig intestine. Mol Pharmacol. 1994 Aug;46(2):256–265. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES