Úloha metabolitů kyseliny arachidonové cestou cytochromu P-450 v patogenezi hypertenze

• Main Author: Čertíková-Chábová, Věra
• Other Authors: Tesař, Vladimír
• Format: Doctoral Thesis
• Language: Czech
• Published: 2008
• Online Access: http://www.nusl.cz/ntk/nusl-291441

Background: 20-HETE and EETs, metabolites derived from arachidonic acid by cytochrome P-450 (CYP), are part of the effector mechanisms in the renin-angiotenzin-aldosterone system. They regulate vasoconstriction/ vasodilation and natriuresis and thus contribute to the regulation of blood pressure. Hypertensive rats transgenic for mouse Re-2 renin gene (TGR) are a good model for hypertension caused by a single gene and very suitable for the study of the role20-HETE and EETs in vivo. Hypothesis: Abnormal production and/or activity of 20-HETE and EETs contributes to the development and or/maintenance of high blood pressure in TGR. Materials and methods: Hypertensive TGR heterozygous males of various ages weres studied. Normotensive HanSD animals (the same genetic background without Ren-2 gene) were used as controls. Three complex studies were performed: Study 1: Chronic inhibition of CYP with non-selective inhibitors 1- aminobenzotriazol (ABT) and CoCl2 in young prehypertensive and adult hypertensive animals and respective controls. Study 2: Acute experiments with selective inhibitors N-metyl-sulfonyl- 12,12-dibromododec-11- enamide (DDMS) and N-metylsulfonyl-6-(2- propargyloxyfenyl)-hexamide MS-PPOH. Study 3: Chronic selective inhibition of 20-HETE production by DDMS and selective inhibition of EETs...