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Myocardial cell signaling in spontaneously hypertensive rats with transgenic and congenic expression of CD36
Klevstigová, Martina ; Nováková, Olga (advisor) ; Kalous, Martin (referee) ; Zicha, Josef (referee)
Long-chain fatty acids (LCFA) are the primary energy source in the myocardium and an imbalance in the LCFA and glucose utilization could cause cardiovascular diseases. More than 50% of LCFA uptake by the heart is mediated by the fatty acid translocase CD36 and disruption of its function has been shown to impair cardiovascular functions. The spontaneously hypertensive rat (SHR) harbors a deletion variant of the Cd36 gene that results in reduced LCFA transport into myocytes. Therefore, the main aim of this thesis was to investigate the importance of a functional CD36 to sustain normal physiological functions of the heart. We used SHR and two genetic modified SHR strains, the congenic SHR-4 and the transgenic SHR-Cd36, with fully functional CD36. They differ in the CD36 expression and in the manner how they were derived from the SHR. CD36 has been proven to play a role in the pathogenesis of insulin resistance. Therefore we analyzed the effect of a functional CD36 on insulin resistance and protein kinase C (PKC) expression, which is known to be involved in the mechanism of insulin resistance, in the heart of SHR-4 and SHR. We showed that the SHR-4 had lower serum free fatty acids (FFA) and triacylglycerols (TAG) concentrations, indicating improved insulin sensitivity. Furthermore, SHR-4 had increased...
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The role of RhoA/Rho kinase signalling pathway in the regulation of blood pressure in normotensive and hypertensive rats
Brunová, Aneta ; Zicha, Josef (advisor) ; Wasková, Petra (referee)
Evidence is accumulating that point to a major role of Rho kinase in arterial pathophysiology. Rho kinase is a key enzyme in calcium sensitization in vascular smooth muscle cells. Calcium sensitization is characterized as an increase in vascular contractility in the conditions of constant cytosolic calcium level. Inhibitors of Rho-kinase exert beneficial effects on the cardiovascular system, mainly by lowering vascular contractility. This thesis summarizes the current progress in understanding of the signaling pathways involved in the control of peripheral resistance of spontaneously hypertensive rats (SHR). It is evident that enhanced sympathetic activity and abnormal regulation of ion channel activity collectively contribute to high blood pressure maintenance in SHR.
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L-serine induced effects on blood pressure in normotensive and hypertensive rats: the influence of anesthesia
Bencze, Michal ; Zicha, Josef (advisor) ; Husková, Zuzana (referee)
Anesthetics cause profound alterations in respiratory and cardiovascular systems. Our experiments demonstrated that different anesthetics caused different changes in blood pressure regulating components. The role of particular BP regulating systems was disclosed by their selective inhibition - sympathetic nervous system blocked by pentolinium (peripheral ganglionic blockade), renin-angiotensin system by captopril (angiotensin converting enzyme blocker) and nitric oxide production by L-NAME (nitric oxide synthase blocker). Components of blood pressure regulating mechanisms in conscious normotensive Wistar rats and spontaneously hypertensive rats were compared with four different groups of anesthetized rats by pentobarbital, ketamine-xylazine, chloralose-urethane and isoflurane. Each anesthesia caused different hemodynamic changes. If hemodynamic conditions should be similar to conscious rats, the most suitable anesthetic is pentobarbital. L-serine-induced effects represent endothelium-derived hyperpolarizing factor (EDHF)-mediated response, which is a type of endothelium-dependent regulation of vascular tone, independent of nitric oxide and prostacyclin production. Pronounced L-serine effects on blood pressure were shown in NO-deficient type of hypertension. Our study demonstrated its pronounced effects in...
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Feeding artery of vascular accesses for hemodialysis: model of arterial adaptation to high blood flow
Tuka, Vladimír ; Malík, Jan (advisor) ; Vízek, Martin (referee) ; Zicha, Josef (referee)
Background: Arteries adapt their diameter to changing haemodynamic conditions to maintain constant wall shear stress, the force generated by flowing blood on endothelial cells. The feeding artery of haemodialysis vascular accesses is a human model of arterial adaptation to chronically high blood flow and thus to high wall shear stress. The process of arterial adaptation is endothelium dependent. Endothelial dysfunction related to End-Stage Renal Failure, diabetes mellitus, dyslipidemia may impair also the dilatation of the feeding artery of vascular accesses. First the review of the literature presents in three parts different aspects of arterial adaptation: 1) arterial adaptation with focusing on the role of haemodynamic factors, 2) the influence of end-stage renal disease on arterial adaptation, 3) feeding artery of vascular accesses as a model of arterial response to chronic increase in blood flow. Methods: We examined the feeding artery of radial and brachial polytetrafluoroethylene grafts shortly after and one and two years after access creation. We used duplex ultrasonography to obtain internal diameter and blood velocity in the feeding arteries. We calculated wall shear rate as 4 x blood velocity / internal diameter and used it as approximation of wall shear stress. Results: In the first study we...
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