Cytochrome P-450 ω-hydroxylase: A potential O2 sensor in rat arterioles and skeletal muscle cells

Mary Pat Kunert, Richard J. Roman, Magdalena Alonso-Galicia, J R Falck, Julian H. Lombard

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Abstract

The purposes of this study were to 1) further evaluate the possible role that vasoconstrictor metabolites of cytochrome P-450 (CYP) ω-hydroxylase plays in O2-induced constriction of arterioles in the rat skeletal muscle microcirculation, 2) determine whether ω-hydroxylases are expressed in rat cremaster muscle, and 3) determine whether the enzyme is located in the parenchyma or the arterioles. O2-induced constriction of third-order arterioles in the in situ cremaster muscle of Sprague-Dawley rats was significantly inhibited by the CYP inhibitors N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 50 μM) and 17-octadecynoic acid (ODYA; 10 μM). Immunoblot analysis with antibody raised against CYP4A protein indicated the presence of immunoreactive proteins in the cremaster muscle and in isolated arterioles and muscle fibers from this tissue. However, the molecular mass of the immunoreactive proteins was 85 kDa instead of the expected 50-52 kDa for CYP4A ω-hydroxylase isolated from rat liver or kidney. Treatment of the cremaster muscle with deglycosidases shifted the bands to the expected range which indicates that these proteins are likely glycosylated in skeletal muscle. Immunohistochemistry revealed intense staining of both muscle fibers and microvessels in the cremaster muscle. The results of this study indicate that O2 sensing in the skeletal muscle microcirculation may be mediated by CYP4A ω-hydroxylases in both arterioles and parenchymal cells.

Original languageEnglish (US)
Pages (from-to)H1840-H1845
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number4 49-4
StatePublished - Apr 1 2001

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Keywords

  • 20-hydroxyeicosatetraenoic acid
  • Autoregulation
  • Microcirculation
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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