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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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The role of adrenergic system in genetic hypertension
Loučková, Anna ; Kadlecová, Michaela (advisor) ; Husková, Zuzana (referee)
The adrenergic system plays an important role in the regulation of blood pressure. In the spontaneously hypertensive rat, the most studied model of essential hypertension, many components of the adrenergic system are altered. Changes in expression level of any catecholamine biosynthetic enzymes or any adrenergic receptor subtypes could be one of the causes of hypertension development. In this work, the expression of adrenergic system genes was measured in adrenal gland, renal cortex and renal medulla of the spontaneously hypertensive (SHR), Wistar-Kyoto and Brown Norway rats at the age of thirteen weeks. In adrenal gland of SHR, all four catecholamine biosynthetic enzymes (tyrosine hydroxylase, DOPA decarboxylase, dopamine β-hydroxylase and phenylethanolamine-N- methyltransferase) and almost all subtypes of adrenergic receptors (with the exception of Adra1a and Adra1d) were underexpressed. This generally decreased expression in adrenal gland of SHR suggests that at least a part of regulation of adrenergic system gene expression is common. The mechanism of this downregulation in SHR could be a negative feedback through adrenergic receptors stimulated by high plasma noradrenaline concentration. In the kidney of SHR, there were no differences in the expression of most of adrenergic receptor subtypes with the...
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Synchronization of peripheral circadian clocks during ontogenesis.
Paušlyová, Lucia ; Sumová, Alena (advisor) ; Hock, Miroslav (referee)
The circadian system is an important coordinator of physiological functions of a mammalian organism. It comprises of a central oscillator represented by cells in the suprachiasmatic nuclei of hypothalamus (SCN) and peripheral oscillators in most if not all cells of peripheral tissues. The peripheral oscillators, similarly to the central ones, generate circadian oscillations at the level of so called clock genes and their protein products. In peripheral tissues, oscillations in expression of the individual clock genes are autonomous, however, they need to be synchronized to ensure their robust rhythmic expression. The peripheral clocks are synchronized mainly by rhythmical signals from the SCN, including signals regulating food intake. Disturbances in the clock gene expressions, as well as impaired synchronization signals, can result in various pathophysiological states. Spontaneously hypertensive rat (SHR) strain is a convenient animal model to study potential connection between the disturbed circadian system and progressive development of hypertension and metabolical diseases in mammals. Various studies have shown differences in the rhythmical expression of clock genes between SHR strain and normotensive Wistar/Wistar-Kyoto strain. The aim of this thesis is to provide insight into the early...
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The role of adrenergic system in genetic hypertension
Loučková, Anna ; Kadlecová, Michaela (advisor) ; Husková, Zuzana (referee)
The adrenergic system plays an important role in the regulation of blood pressure. In the spontaneously hypertensive rat, the most studied model of essential hypertension, many components of the adrenergic system are altered. Changes in expression level of any catecholamine biosynthetic enzymes or any adrenergic receptor subtypes could be one of the causes of hypertension development. In this work, the expression of adrenergic system genes was measured in adrenal gland, renal cortex and renal medulla of the spontaneously hypertensive (SHR), Wistar-Kyoto and Brown Norway rats at the age of thirteen weeks. In adrenal gland of SHR, all four catecholamine biosynthetic enzymes (tyrosine hydroxylase, DOPA decarboxylase, dopamine β-hydroxylase and phenylethanolamine-N- methyltransferase) and almost all subtypes of adrenergic receptors (with the exception of Adra1a and Adra1d) were underexpressed. This generally decreased expression in adrenal gland of SHR suggests that at least a part of regulation of adrenergic system gene expression is common. The mechanism of this downregulation in SHR could be a negative feedback through adrenergic receptors stimulated by high plasma noradrenaline concentration. In the kidney of SHR, there were no differences in the expression of most of adrenergic receptor subtypes with the...
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Role of mitochonodrial genome in myocardial ischemia-reperfusion injury of spontaneously hypertensive rats (SHR) adapted to hypoxia.
Brabcová, Iveta ; Žurmanová, Jitka (advisor) ; Mlejnek, Petr (referee)
Diplomová práce Abstract - Iveta Brabcová Abstract Ischemia-reperfusion heart injury is one of the most significant diseases affecting mankind and therefore current research pays more attention to its prevention and knowledge of the possible mechanisms which protect the heart. Adaptation to hypoxia has been known for several decades as a cardioprotective intervention but the main issues of protective mechanisms which are induced by the adaptation are still not completely understood. An important role of mitochondria as the main producers of energy and reactive oxygen species which can play a signalizing role in these mechanisms is confirmed in many studies. For this reason a special conplastic strain SHR/OlaIpcv-mtBN/Crl was created. This strain carries the nuclear genome of spontaneously hypertensive rat (SHR) and the mitochondrial genome of normotensive, highly resistant strain Brown Norway (BN). The aim of this study was to compare the expression of selected gene transcripts in the area of energy metabolism, of genes which are related to mitochondrial biogenesis and signaling and antioxidant systems. Comparing the expression was analyzed between strains and after chronic hypoxia adaptation, which cause cardioprotective phenotype in both of these strains. Our results showed a different expression HIF-1α...
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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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