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  • Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension
    Ljuca, Farid ; Drevenšek, Gorazd ; Zerem, Enver
    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 not450 (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.
    Source: Bosnian journal of basic medical sciences. - ISSN 1512-8601 (Vol. 11, issue 2, 2011, str. 84-86)
    Type of material - article, component part
    Publish date - 2011
    Language - english
    COBISS.SI-ID - 28754649

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