Author/Editor		Ljuca, Farid; Drevenšek, Gorazd; Zerem, Enver
Title		Contribution of Ras farnesyl transferase, MAP kinase and cytochrome P-450 metabolites to endothelin-1 induced hypertension
Type		članek
Source		Bosn J Basic Med Sci
Vol. and No.		Letnik 11, št. 2
Publication year		2011
Volume		str. 84-6
Language		eng
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 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.
Descriptors		HYPERTENSION ENDOTHELIN-1 CYTOCHROME P-450 CALMODULIN-DEPENDENT PROTEIN KINASES FARNESOL TRANSFERASES CYCLOOXYGENASE INHIBITORS LIPOXYGENASE INHIBITORS ANALYSIS OF VARIANCE RATS, SPRAGUE-DAWLEY