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Cytochrome P450 2C is an EDHF synthase in coronary arteries

Author

Listed:
  • Beate Fisslthaler

    (Institut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7)

  • Rüdiger Popp

    (Institut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7)

  • Ladislau Kiss

    (Zentrum der Inneren Medizin, Justus Liebig Universität Gießen)

  • Michael Potente

    (Institut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7)

  • David R. Harder

    (Cardiovascular Research Center, Medical College of Wisconsin)

  • Ingrid Fleming

    (Institut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7)

  • Rudi Busse

    (Institut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7)

Abstract

In most arterial beds a significant endothelium-dependent dilation to various stimuli persists even after inhibition of nitric oxide synthase and cyclo-oxygenase. This dilator response is preceded by an endothelium-dependent hyperpolarization of vascular smooth muscle cells, which is sensitive to a combination of the calcium-dependent potassium-channel inhibitors charybdotoxin and apamin, and is assumed to be mediated by an unidentified endothelium-derived hyperpolarizing factor (EDHF)1,2. Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by β-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of EDHF-mediated relaxation in the porcine coronary artery, and CYP 2C8/34 fulfils the criteria for the coronary EDHF synthase.

Suggested Citation

  • Beate Fisslthaler & Rüdiger Popp & Ladislau Kiss & Michael Potente & David R. Harder & Ingrid Fleming & Rudi Busse, 1999. "Cytochrome P450 2C is an EDHF synthase in coronary arteries," Nature, Nature, vol. 401(6752), pages 493-497, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6752:d:10.1038_46816
    DOI: 10.1038/46816
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