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Excitation-Contraction and Excitation-Transcription Coupling in Vascular Smooth Muscle Cells: Alterations in Experimental Hypertension and Vascular Remodeling
Misárková, Eliška ; Zicha, Josef (advisor) ; Hock, Miroslav (referee)
Vascular smooth muscle cells (VSMCs) express considerable phenotype plasticity. They are able to change their phenotype in vivo if necessary. It is important to know that during this phenotype switch the expression of transport proteins and channels is modified, which results in significant alteration of Ca2+ signaling in smooth muscle cells. In differentiated cells, which represent contractile phenotype, there are dominant rapid, transient events in intracellular Ca2+ concentration (Ca2+ i), while the resting cytosolic Ca2+ i concentration is low. In differentiated cells these Ca2+ i events are mainly caused by two components of the Ca2+ signalling pathways: 1) extracellular Ca2+ influx via L-type voltage-gated Ca2+ channels (L-type VGCC) in plasma membrane, and 2) depletion of intracellular Ca2+ stores via ryanodin receptors located on sarcoplasmic reticulum. Rapid Ca2+ i oscillations are quickly reduced by numerous Ca2+ ATPases of sarco/endoplasmic reticulum and plasma membrane. Proliferating vascular smooth muscle cells are characterized by a long-lasting Ca2+ i oscillations accompanied by sustained elevation of basal intracellular Ca2+ concentration. During phenotype switch from contractile phenotype to proliferative phenotype there is decreased Ca2+ ATPase activity, and store-operated Ca2+...
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Awareness of overweight people and people without overweight on the risk of cardiovascular dise
Hladíková, Lenka ; Marádová, Eva (advisor) ; Hanušová, Jaroslava (referee)
This thesis deals with awareness of overweight and non-overweight people about of the risk of cardiovascular diseases. The goal is to determine the level of knowledge of both groups in the section of cardiovascular diseases and their interest in this issue. Next goal is to determine the degree of difference in awareness in this issue between the sexes. The theoretical part provides information about obesity (causes, symptoms, complications, treatment). It also deals with frequent cardiovascular diseases - hypertension, atherosclerosis, myocardial infarction, ischemic heart disease, cerebrovascular accident, and dyslipidemia. One of chapters is devoted to projects that address prevention of obesity and cardiovascular diseases. The practical part of work describes examined group that participated in the survey. Analysis of the results shows that people who are not overweight or obese are more informed about the risks of cardiovascular disease than overweight and obese people, because they are less interested in this issue. Women are better informed in the section of cardiovascular diseases than men. 14 individuals out of 89 members of research is interested in the issue of cardiovascular diseases. Only 12 individuals is adequately informed of the issue of cardiovascular disease. Work includes eating plan...
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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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The effect of chronic hypoxia on cardiac ischemic tolerance of spontaneously hypersensitive rats
Zajíčková, Pavlína ; Neckář, Jan (advisor) ; Žurmanová, Jitka (referee)
The goal of this thesis was to discover the influence of adaptation to chronic hypoxia on ischemic tolerance of heart - this experiment was carried out on two different hypertension kinds of laboratory rats. Spontaneously hypertensive rats (SHR) and rats from a conplastic strain SHR/OlaIpcv-mtBN/Crl , whose mitochondrial genome of the SHR strain was replaced with a mitochondrial genome of the normotensive strain Brown Norway, were exposed to continuous normobaric hypoxia (10% O2) for a period of 3 weeks. On the other hand, the control group of rats was kept in normoxia. At the end of the adaptation period, the ischemic tolerance of heart and the mitochondrial aconitase expression were examined. In the case of both hypertensive strains, the chronic hypoxia led to a significant drop in the size of a myocardial infarction and also to a drop in the number of reperfusion arrhythmias. In the case of the SHR strain, the incidence of ischemic arrhythmias decreased. Chronic hypoxia had no impact on the aconitase expression for both analysed strains. This thesis showed that the ischemic tolerance of heart can be enhanced in the case of the SHR strain. On the other hand, the mitochondrial genome of the SHR strain does not seem to play any significant role in protection mechanism. Key words: chronic hypoxia,...
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Endothelin system and the role of salt in hypertension
Čejková, Soňa ; Vaněčková, Ivana (advisor) ; Soták, Matúš (referee)
Although hypertension is studied for several decades, this problem is still not solved. Moreover, its incidence increases. Most cases of secondary hypertension is associated with the kidneys, the most important organ regulating the volume and ionic composition of body fluids. If the kidneys are damaged, or intake of salt is excessive, they are unable to fulfill their role and blood pressure (BP) increases. Especially salt contributes to secondary hypertension. Excessive salt intake increases the volume of body fluids and subsequently increases BP, and secondary act on the mechanisms regulating BP, mainly the renin-angiotensin system (RAS) and endotelin (ET) system. Endothelin-1 (ET 1) is the main active peptide of the ET system. ET-1 is one of the most potent vasoconstrictors. It acts through ET receptors type A and B (ETA and ETB receptors), which belong to the family of receptors coupled with G-proteins. The effects of ETA and ETB receptors differ depending on the type of cells where they are located. For example, ETB receptors in vascular smooth muscle contribute to vasoconstriction, whereas the same receptors on endothelial cells of blood vessels mediate vasodilation (stimulating the production of NO). In the kidney, ET system affects excretion of Na+and water and contribute to the regulation...
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Evaluation of results using different methods of experimental measuring of blood pressure amongst students of the First Faculty of Medicine of the Charles University
Sova, Jan ; Kymplová, Jaroslava (advisor) ; Jirsa, Jan (referee)
During the projects from biophysics of freshman students of the Faculty of Medicine the pressure measurement is run by several different methods; palpation, auscultatory and digital method. Students are learning to record the measurement in a systematic way, and they are learning to compare the results of every method to each other. The measurement of systolic and diastolic pressure are dependent on each other of course, as well they are dependent on the set of biometric and other information that is well available in healthy students (sex, height, weight, physical strain etc.). The aim of the thesis is to compare the results acquired by the methods of measurement mentioned above, related to the accuracy of the scattering of the measurement and related to the anticipated standard values of healthy individuals. The basis of the thesis is going to be project and creation of the regression model for the levels of systolic/diastolic pressure measured out that is dependent on biometric data along with the testing of statistical importance of parametres through the procedure of multifactorial ANOVA for the repeated measurement. The result will aim to show both advantages and disadvantages of different methods of the pressure measurement during accordingly varying conditions of experiments. The thesis...
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The enzymes of catecholamine metabolism in experimental hypertension.
Loučková, Anna ; Kuneš, Jaroslav (advisor) ; Klevstigová, Martina (referee)
Catecholamines dopamine, norepinephrine and epinephrine are significantly involved in regulation of blood pressure. The most important enzymes participating in their metabolism are tyrosin hydroxylase, DOPA dekarboxylase, dopamine β-hydroxylase and phenylethanolamine N-methyltransferase. This thesis summarizes current knowledge about these enzymes, focusing on their role in the development of essential hypertension. Experimental models are often used in the study of hypertension because of their practical and ethic reasons. Most findings were obtained in spontaneously hypertensive rats, due to their similarity to human essential hypertension. Metabolism of catecholamines in spontaneously hypertensive rat differs in many aspects from that of normotensive controls. The primary cause of this type of hypertension has not yet been distinguished from compensatory responses. However, prevention or slow-down the disease-development process can be achieved by various interventions. This information may help to identify new treatments for human hypertension.
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Applications of chiral and achiral chromatography in pharmacology and toxicology
Chytil, Lukáš ; Slanař, Ondřej (advisor) ; Bultas, Jan (referee) ; Coufal, Pavel (referee)
Development and validation of methods for analysis of several drugs or their metabolites are decribed in this thesis. The document is presented as a commentary to the original papers, which were published in peer reviewed journals. Discussion on the optimization of each method is presented and covers also method development and influence of preanalytical aspects. Additionally, examples of the application of the developed methods in clinical pharmacology and toxicology are shown. This dissertation consists of three parts: enantiomeric determination of tramadol and its metabolite, determination of some antihypertensive drugs, and qualitative analysis of benzodiazepines. Development of a method for chiral analysis of tramadol and its desmethylated metabolite O- desmethyltramadol (ODT) in human urine and plasma is described in the first part of the thesis. Tramadol is a centrally acting analgetic drug, which is used as racemate in clinical practise. Each enantiomer displays different binding properties for various receptors: (+)-tramadol preferentially inhibits serotonin reuptake while (-)-tramadol mainly inhibits noradrenalin reuptake. (+)-tramadol is considered 10-times more potent than (-)-tramadol. Major active metabolite (ODT), which is considered to be the main agent responsible for the...
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Left ventricle remodeling in patients with primary aldosteronism and essential hypertension
Indra, Tomáš ; Holaj, Robert (advisor) ; Ošťádal, Petr (referee) ; Paleček, Tomáš (referee)
Myocardial damage is one of the most serious consequences of arterial hypertension. Changes in the heart structure and function develop not only due to pressure overload itself, but many other hemodynamic and neurohumoral factors contribute to their formation. Our work has compared echocardiohraphic strucutural anf functional changes of the left ventricle, caused by essential hypertension and hypertension associated with primary aldosteronism (PA) as the most common reason for secondary hypertension. The first part of our work focused on the differences in left ventricle geometry in men with PA and essential hypertension after separating it's low-renin form (where, similarly to PA, the plasma volume expansion was considered to have the dominant effect on left ventricle remodelation). In men with low-renin forms of hypertension including PA, we observed greater both endsystolic and enddiastolic diameter of the left ventricle, lower relative wall thickness and more frequent eccentric type of hypertrophy when compared to essential hypertensives with normal renin levels. Whereas left ventricle cavity diameters were positively correlated to aldosterone levels, wall thicknesses were associated mainly with hypertension severity expressed as an average 24hour blood pressure and number of antihypertensives....
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