Introduction: Two major product groups originate from the arachidonic acid metabolic pathway of cytochromes P450: epoxyeicosatrienoic acid (EETs) and 19 and 20-hydroxyeicosatetraenoic acid (19- and 20-HETE). These metabolites play an important role in the regulation of blood pressure, inflammatory responses, regulation of sodium excretion and other crucial physiological processes. Hypothesis: Our studies were based on the hypothesis that abnormalities in the production and function of these cytochrome P450 metabolites significantly contribute to the pathophysiology of hypertension development, in particular in the angiotensin II-dependent models. Objective: To investigate if the increased bioavailability of the above-mentioned metabolites in the kidney tissue will result in blood pressure reduction in the ANG II - dependent rat model of hypertension. Methods: The two methods to increase the concentration of EETs was chosen. In the first part of the study, we administered a soluble epoxide hydrolase inhibitor cAUCB [cis-4- [4- (3-adamantan-1-yl- ureido) cyclohexyloxy] benzoic acid, at a dose of 26 mg.l-1 administered in drinking water], an enzyme responsible for inactivation of biologically active forms of EETs. In the second series of the experiments we applied a synthetic EET analogue, called...
| Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:436095 |
| Date | January 2020 |
| Creators | Jíchová, Šárka |
| Contributors | Červenka, Luděk, Zicha, Josef, Štengl, Milan |
| Source Sets | Czech ETDs |
| Language | Czech |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis |
| Rights | info:eu-repo/semantics/restrictedAccess |
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