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The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Polák, Jan (referee) ; Babula, Petr (referee)
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
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Myocardial beta-adrenergic signaling during adaptation of rats to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Ostašov, Pavel (referee)
Endogenous cardiac protection against acute ischemia/reperfusion injury can by increased by cardiac adaptation to various forms of chronic hypoxia. Chronic hypoxia induces a large variety of adaptive changes in the myocardium that could be considered as protective, but the exact mechanism of increased ischemic tolerance is unknown. Different studies suggest that catecholamine release and their effect on -adrenergic signaling after adaptation to chronic hypoxia contributes to cardioprotection. In this study we focused on characterization of -adrenergic receptors ( -ARs) in the myocardium of rats after adaptation to three different hypoxic conditions: 1. intermittent normobaric hypoxia - INH/R (23 h hypoxia, 1 h reoxygenation), 2. intermittent normobaric hypoxia - INH (8 h hypoxia, 16 h normoxia), 3. continuous normobaric hypoxia - CNH (24 h hypoxia). We compared how each hypoxic model affects the total number of -adrenergic receptors and proportion of individual subtypes ( 1-and 2-ARs) in the left and right ventricles compared control normoxic rats. The INH model had apparently no effect on -ARs in either ventricles. On the other hand, adaptation to INH/R and CNH was accompanied by a significant decrease (by about 25%) in the total number of -adrenergic receptors in the right ventricles. Our present...
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The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
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The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
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The role of adrenergic signaling in cardioprotection induced by adaptation to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Polák, Jan (referee) ; Babula, Petr (referee)
Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...
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Neurobiology of hypoxic-ischemic insult in immature brain
Kuchtiak, Viktor ; Valeš, Karel (advisor) ; Hahnová, Klára (referee)
Pathology of the hypoxic-ischemic insult is very well described in the adult age, whereas the state of knowledge is largely neglected during the perinatal age. Serious insult in the early postnatal age leads often to the permanent neurological consequences or death. Ischemic insult causes over release of the glutamate in a brain tissue. This process is followed by excitotoxic damage of the tissue. Glutamatergic NMDA receptors play a key role in the excitotoxicity. Over-activated NMDA receptors are one of the possible therapeutic approaches against ischemic damage of the brain. Speaking of contemporary projects focusing on perinatal stroke, it is necessary to take into account developmental differences in the brain tissue and the requirements to minimal toxicity of possible drugs. Pharmacotherapies for hypoxic-ischemic damage implemented in the current perinatology are insufficients.
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Myocardial beta-adrenergic signaling during adaptation of rats to chronic hypoxia
Hahnová, Klára ; Novotný, Jiří (advisor) ; Ostašov, Pavel (referee)
Endogenous cardiac protection against acute ischemia/reperfusion injury can by increased by cardiac adaptation to various forms of chronic hypoxia. Chronic hypoxia induces a large variety of adaptive changes in the myocardium that could be considered as protective, but the exact mechanism of increased ischemic tolerance is unknown. Different studies suggest that catecholamine release and their effect on -adrenergic signaling after adaptation to chronic hypoxia contributes to cardioprotection. In this study we focused on characterization of -adrenergic receptors ( -ARs) in the myocardium of rats after adaptation to three different hypoxic conditions: 1. intermittent normobaric hypoxia - INH/R (23 h hypoxia, 1 h reoxygenation), 2. intermittent normobaric hypoxia - INH (8 h hypoxia, 16 h normoxia), 3. continuous normobaric hypoxia - CNH (24 h hypoxia). We compared how each hypoxic model affects the total number of -adrenergic receptors and proportion of individual subtypes ( 1-and 2-ARs) in the left and right ventricles compared control normoxic rats. The INH model had apparently no effect on -ARs in either ventricles. On the other hand, adaptation to INH/R and CNH was accompanied by a significant decrease (by about 25%) in the total number of -adrenergic receptors in the right ventricles. Our present...
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The role of protein kinase B in cardioprotective mechanisms
Grešíková, Milada ; Žurmanová, Jitka (advisor) ; Hahnová, Klára (referee)
Cardiovascular disease is the most common cause of death worldwide and therefore it belongs to one of the most widespread diseases of modern civilization. For this reason, cardiovascular research focuses on unraveling mechanisms, which participate in protection of cardiac tissue. Protein kinase B (PKB/AKT) is an important regulator of cellular processes which could play a substantial role in protective mechanisms of the heart. There are 3 known isoforms of PKB/AKT, which differ in their localization and function, nevertheless all of them have an essential role in cardiomyocytes. PKB/AKT is involved in regulation of many cellular functions including cell proliferation, growth and energy metabolism, and it particularly takes part in the regulation of apoptosis. PKB/AKT controls the apoptotic pathway through regulation of pro- and anti-apoptotic proteins, hexokinase II, glycogen synthase kinase 3 and Ca2+ channels, by which it protects mitochondria and cardiomyocytes against cell death. That is why PKB/AKT is the center of attention of today's cardiovascular research and it could become one of the main therapeutic targets in the treatment of ischemia-reperfusion injury.
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