@misc{Kij_Agnieszka_The_2019, author={Kij, Agnieszka}, address={Kraków}, howpublished={online}, year={2019}, school={Wydział Farmaceutyczny}, language={pol}, abstract={In this study, two original bioanalytical methods for quantification of eicosanoids biosynthesised from arachidonic acid (AA) via different metabolic pathways were developed and validated using UPLC-MS/MS technique. The methods allowed to assess the eicosanoid profile in selected animal models of endothelial dysfunction and its changes upon pharmacological modulation of vascular function.In NO-deficient mice, the biosynthesis of eicosanoids formed by cyclooxygenase (COX) was elevated. MNA treatment improved the vessel function by activation of COX-independent mechanisms.In murine model of hypertension, angiotensin II infusion increased the biosynthesis of CYP450- derived 20-HETE. The inhibition of thrombin activity by dabigatran improved the function of endothelium by sustaining the NO bioavailability and reducing the 20-HETE production.The development of 4T1 breast cancer was associated with the elevated biosynthesis of eicosanoids formed by COX and lipoxygenase (LOX) and with the reduced production of CYP450-derived AA metabolites. The inhibition of NO synthase increased the biosynthesis of epoxyeicosatrienoic acids (EET) and 20-HETE, which probably supported the disease progression under NO-deficiency.The obtained results show the heterogeneity of eicosanoid profile in investigated murine models of endothelial dysfunction and the pharmacological modulation of vascular functi}, abstract={on indicates which AA metabolic pathways could be an effective target in the treatment of hypertension and breast cancer.}, title={The assessment of eicosanoid profile in animal models of endothelial dysfunction}, type={Praca doktorska}, keywords={arachidonic acid, hypertension, endothelium, breast cancer, eicosanoids}, }