Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension
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,...
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2011-05-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/2586 |
| _version_ | 1797260842899603456 |
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| author | Farid Ljuca Gorazd Drevenšek Enver Zerem |
| author_facet | Farid Ljuca Gorazd Drevenšek Enver Zerem |
| author_sort | Farid Ljuca |
| collection | DOAJ |
| description | 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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| first_indexed | 2024-04-24T23:31:45Z |
| format | Article |
| id | doaj.art-b566f6ee721148848b2800afb8559801 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:31:45Z |
| publishDate | 2011-05-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-b566f6ee721148848b2800afb85598012024-03-15T14:34:58ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2011-05-0111210.17305/bjbms.2011.2586346Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertensionFarid Ljuca0Gorazd Drevenšek1Enver Zerem2Department of Physiology, University of Tuzla, Faculty of MedicineDepartment of Pharmacology and experimental toxicology, University of Ljubljana, Faculty of MedicineUniversity Clinical Center TuzlaEndothelin 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. https://www.bjbms.org/ojs/index.php/bjbms/article/view/2586endothelin-1hypertensioncytochrome P-450Ras farnesyl transferasemitogen activated protein kinase |
| spellingShingle | Farid Ljuca Gorazd Drevenšek Enver Zerem Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension Biomolecules & Biomedicine endothelin-1 hypertension cytochrome P-450 Ras farnesyl transferase mitogen activated protein kinase |
| title | Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension |
| title_full | Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension |
| title_fullStr | Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension |
| title_full_unstemmed | Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension |
| title_short | Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension |
| title_sort | contribution of ras farnesyl transferase map kinase and cytochrome p 450 metabolites to endothelin 1 induced hypertension |
| topic | endothelin-1 hypertension cytochrome P-450 Ras farnesyl transferase mitogen activated protein kinase |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/2586 |
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