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Role of Potassium Channels in the Regulation of Vascular Smooth Muscle Tone
Bencze, Michal ; Zicha, Josef (advisor) ; Moravec, Jan (referee)
In smooth muscle cells, potassium channels play an important role in the regulation of the membrane potential of smooth muscle cells, which is closely related to vascular tone. Four different types of K+ channels have been described in vascular smooth muscle cells. Voltagegated K+ channels (KV), which can be open by depolarization. Calcium-activated potassium channels (KCa), from the same gene family, are voltage dependent, and can be activated also by elevated concentration of intracellular Ca2+. Inward rectifying channels (KIR) display negative slope conductance. These channels amplify potassium flow and function as an extracellular K+ sensor. ATP-sensitive K+ channels (KATP) channels provide a link between cell metabolism and membrane potential. Function of K+ channels is also important in endothelium, which produces many vasodilatators and vasoconstrictors. Abnormal expression profile of K+ channels is part of vascular cell membrane remodeling.
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The role of calcium influx and calcium sensitization in contraction of isolated arteries of normotensive and hypertensive rat
Bencze, Michal ; Zicha, Josef (advisor) ; Neckář, Jan (referee) ; Chalupský, Karel (referee)
Vascular resistance is mainly determined by the contraction of vascular smooth muscle (VSM), which is regulated by the phosphorylation of myosin light chain (MLC). VSM contraction is initiated by calcium influx into the VSM cells, which is mediated by transient receptor potential (TRP) channels and L-type voltage- dependent calcium channels (L-VDCC). On the other hand, calcium sensitization is a mechanism enhancing vascular contractile response at a given level of intracellular calcium by RhoA/Rho kinase pathway-mediated inhibition of myosin light chain phosphatase. In this thesis I present the data about i) the role of TRP channels in the mechanisms of vascular smooth muscle contraction, ii) enhanced contractility of arteries from spontaneously hypertensive rats (SHR), and iii) the differences in contraction of arteries from normotensive and hypertensive rats related to the role of RhoA/Rho kinase pathway in three types of experimental hypertension (SHR, Ren-2 transgenic rats and salt-sensitive Dahl rats). In the study concerning TRP channels, I compared the effects of three commonly used non-selective TRP channels inhibitors (2-APB, SKF-96365, FFA) on isolated arteries. Among them 2-APB was the most interesting because the observed inhibitory effects of 2-APB were dependent on the type of...
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Role of Potassium Channels in the Regulation of Vascular Smooth Muscle Tone
Bencze, Michal ; Zicha, Josef (advisor) ; Moravec, Jan (referee)
In smooth muscle cells, potassium channels play an important role in the regulation of the membrane potential of smooth muscle cells, which is closely related to vascular tone. Four different types of K+ channels have been described in vascular smooth muscle cells. Voltagegated K+ channels (KV), which can be open by depolarization. Calcium-activated potassium channels (KCa), from the same gene family, are voltage dependent, and can be activated also by elevated concentration of intracellular Ca2+. Inward rectifying channels (KIR) display negative slope conductance. These channels amplify potassium flow and function as an extracellular K+ sensor. ATP-sensitive K+ channels (KATP) channels provide a link between cell metabolism and membrane potential. Function of K+ channels is also important in endothelium, which produces many vasodilatators and vasoconstrictors. Abnormal expression profile of K+ channels is part of vascular cell membrane remodeling.
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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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