Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension

  • Farid Ljuca Department of Physiology, University of Tuzla, Faculty of Medicine
  • Gorazd Drevenšek Department of Pharmacology and experimental toxicology, University of Ljubljana, Faculty of Medicine
  • Enver Zerem University Clinical Center Tuzla
Keywords: endothelin-1, hypertension, cytochrome P-450, Ras farnesyl transferase, mitogen activated protein kinase

Abstract

Endothelin 1 (ET-1) is vasoactive peptide that acts via ET-A receptors coupling inducing vascular smooth muscle cell proliferation and contraction. ET-1 is involved in the development and maintenance of hypertension.

Aim of this study was to determine the contribution of Ras farnesyl transferase, mitogen activated protein kinase (MAP kinase) and cytochrome P¬450 (CYP450) metabolites to ET-1 induced hypertension.

ET-1 (5 pmol/kg per minute) was chronically infused into to the jugular vein by use of mini-osmotic pump for 9 days in male Sprague-Dawley rats. Mean arterial blood pressure (MABP) in ET-1-treated rats was 154±2 mm Hg (hypertensive rats) compared with 98±3 mm Hg in control (normotensive) rats. Infusion of Ras farnesyl transferase inhibitor FPTIII (138 ng/min), MAP kinase inhibitor PD-98059 (694 ng/min) and CYP450 inhibitor 17-ODYA (189 ng/min) significantly attenuated MABP to 115±2.5 mm Hg, 109±3 mm Hg and 118±1.5 mm Hg, respectively. These results suggest that CYP-450 metabolites and Ras/MAP kinase pathway contribute to the development of ET-1 induced hypertension. Further investigation has to be done to confirm whether activation of RAS/MAP kinase pathway by arachidonic acid metabolites plays an important role in the development of ET-1 induced hypertension.

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Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension
Published
2011-05-20
How to Cite
1.
Ljuca F, Drevenšek G, Zerem E. Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension. Bosn J of Basic Med Sci [Internet]. 2011May20 [cited 2020Oct.1];11(2):84-6. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2586
Section
Biochemistry