Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites

R. C. Harris, K. A. Munger, K. F. Badr, K. Takahashi

Research output: Contribution to journalArticle

Abstract

In the rat, intrarenal infusion of epidermal growth factor decreases renal blood flow and glomerular filtration rate, and epidermal growth factor (EGF) induces contraction of cultured rat mesangial cells. The present studies examined the role of arachidonic acid metabolites in this response. Intrarenal EGF infusion increased urinary iPGF by 300%, and in isolated glomeruli EGF stimulated iPGF by 38%, but did not affect thromboxane B2 production. Furthermore, the thromboxane A2 receptor antagonist, SQ29548, did not block EGF's vasoconstrictive effects. After selective cyclooxygenase inhibition with ibuprofen, intrarenal EGF infusion no longer produced local vasoconstriction but instead led to systemic vasodilation (SBP: 117 ± 10 vs. 98 ± 7; n = 5; P <0.05) that was accompanied by significant increases in RPF (3.8 ± 0.4 vs. 5.6 ± 0.2; P <0.01) and glomerular filtration rate (0.9 ± 0.1 vs. 1.1 ± 0.1; P <0.05). When total arachidonate metabolism was inhibited by the additional administration of 5,8,11,14-eicosatetraynoic acid, the EGF-induced vasodilation observed during cyclooxygenase inhibition alone was abolished, and vasoconstrictor responses to EGF were again noted. Similar effects were noted with concomitant administration of the C-P450 inhibitor ketoconazole. EGF's vasoconstrictive effects were unaltered by the simultaneous administration of the angiotensin II antagonist saralasin. Thus, the renal hemodynamic responses to EGF are mediated in part by arachidonic acid metabolites. Cyclooxygenase inhibition unmasks a potent renal and systemic vasodilator action of EGF owing to its stimulation of systemic release of noncyclooxygenase arachidonate metabolites.

Original languageEnglish (US)
Pages (from-to)1654-1660
Number of pages7
JournalFASEB Journal
Volume4
Issue number6
StatePublished - Apr 1 1990
Externally publishedYes

Keywords

  • Arachidonic acid
  • Cyclooxygenase
  • Cytochrome P450
  • Epidermal growth factor
  • Renal hemodynamics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Harris, R. C., Munger, K. A., Badr, K. F., & Takahashi, K. (1990). Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites. FASEB Journal, 4(6), 1654-1660.