Endothelin-1 Induced Vascular Smooth Muscle Cell Proliferation is Mediated by Cytochrome P-450 Arachidonic Acid Metabolites

  • Farid Ljuca Department of Physiology, Faculty of Medicine, University of Tuzla
  • Gorazd Drevenšek Department of Pharmacology and experimental toxicology, Faculty of Medicine, University of Ljubljana
Keywords: endothelin-1, vascular smooth muscle cell proliferation, cytochrome P-450, arachi- donic acid

Abstract

Endothelins (ETs) are a family of three peptides (ET-1, ET-2, ET-3) that are implicated in the physiological control of vascular smooth muscle cell (VSMC) and myocardial contractility and growth. ET-1 is vasoactive peptide that acts via ET-A receptors coupling inducing vascular smooth muscle cell contraction. ET-1 is involved in the development and maintenance of hypertension.

Aim of this study was to investigate whether ET-1 can induce vascular smooth muscle cell proliferation through arachidonic acid (AA) metabolites formed via cytochrome P-450 (CYP-450). VSMC proliferation was measured by [3H]thymidine incorporation in cultured cells treated by ET-1 (10 to l00 nmol/L) in presence of different inhibitors of CYP-450 (17-ODYA 5 μmol/L), lipoxygenase (LO) (baicalein 20 μmol/L) and cyclooxygenase (COX) (indomethacin 5 μmol/L). ET-1 (10 to 100 nmol/L) induced VSMC proliferation and this effect was attenuated by CYP-450 inhibitor (17-ODYA) and lipoxygenase (LO) inhibitor (baicalein) but not by cyclooxygenase (COX) inhibitor (indomethacin). CYP-450 and LO metabolites of AA, 20-hydroxyeicosatetraenoic acid (HETE) and 12-HETE increased [3H]thymidine incorporation in VSMC. Inhibitors of MAP kinase (PD-98059 50 μmol/L) and cPLA2 (MAFP 50 μmol/L) attenuated ET-1 as well as 20-HETE induced VSMC proliferation. These results suggest AA metabolites via CYP-450 mediates ET-1 induce VSMC proliferation.

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Endothelin-1 Induced Vascular Smooth Muscle Cell Proliferation is Mediated by Cytochrome P-450 Arachidonic Acid Metabolites
Published
2010-08-20
How to Cite
1.
Ljuca F, Drevenšek G. Endothelin-1 Induced Vascular Smooth Muscle Cell Proliferation is Mediated by Cytochrome P-450 Arachidonic Acid Metabolites. Bosn J of Basic Med Sci [Internet]. 2010Aug.20 [cited 2020Sep.29];10(3):223-6. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2691
Section
Biochemistry