Search for: [Abstract = "Sphingosine kinase 1 \(Sphk1\) is an enzyme responsible for the synthesis of sphingosine\-1\-phosphate \(S1P\), which acts through mechanisms dependent on specific membrane receptors \(S1prs\) or as an intracellular messenger and affects cardiovascular homeostasis. Imbalance in S1P synthesis and signaling may lead to the development of several cardiovascular pathologies including arterial hypertension. Depending on its localisation and induced signalling cascade, S1P acts as a vasoconstrictor or as a vasodilator, hence previous studies indicate an ambiguous role of Sphk1\/S1P axis modulation in the development of arterial hypertension. However, several independent studies have clearly demonstrated that mice with global deletion of Sphk1 develop less severe hypertension in response to angiotensin II \(AngII\) infusion compared to wild type mice. The aim of this thesis was to investigate the effects of administration of a pharmacological selective Sphk1 inhibitor, PF543, on the development of hypertension and associated left ventricular hypertrophy, to assess therapeutic potential of this inhibitor. Studies revealed that chronic administration of PF543 significantly improves the vasodilatory capacity of mesenteric arteries in hypertensive mice. However, this improvement of endothelial function had no significant effect on systolic blood pressure level in mice. Studies also demonstrated th"]

Number of results: 1