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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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Contribution of particular vasoactive systems in the development of chronic kidney disease
Drábková, Natálie ; Vaněčková, Ivana (advisor) ; Vaňourková, Zdeňka (referee)
Chronic kidney disease (CKD) is a life-threating disease which arises as a frequent consequence of diabetes and hypertension. Since it is going on silently, CKD often progresses to the end-stage renal disease. It is therefore necessary to combat this disease especially due to the fact that the world population is growing old. The aim of this work was to determine the contribution of selected vasoactive systems contributing to the maintenance of high blood pressure in the developmental and established phase of CKD. Two models of CKD were used: 5/6 nephrectomy in Ren-2 transgenic rats (TGR) and stenosis of renal artery (2K1C) in Wistar rats. We demonstrated that renin-angiotensin system does not play so important role in blood pressure maintenance in both CKD models. By contrast, a more important role has sympathetic nervous system. During both the developmental and established phase of CKD, vasoconstrictor systems prevail above vasodilator NO-synthase effects. In fact, the role of NO-dependent vasodilation gradually decreased in nephrectomized TGR rats, while it was unchanged in Wistar rats with 2K1C hypertension.
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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra ; Neckář, Jan (advisor) ; Nováková, Olga (referee) ; Vaněčková, Ivana (referee)
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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Genetic and molecular mechanisms of arterial hypertension in relation to chronic inflammation, oxidative stress, and chronic kidney disease
Krajčoviechová, Alena ; Cífková, Renata (advisor) ; Widimský, Jiří (referee) ; Vaněčková, Ivana (referee)
This thesis provides an appraisal of the structure of clustering of metabolic phenotypes and evaluates the pathophysiological mechanisms underlying the relationship between urinary uric acid and albumin excretion. Two population-based studies were involved. In the first part, we used data obtained in a large representative cross-sectional survey in the Czech Republic (Czech post-MONICA study). We showed that the urinary albumin/creatinine ratio (uACR) was an independent factor for an increase in serum uric acid (SUA) levels in adults without manifest metabolic syndrome (MetS), but with 1-2 MetS component(s). Furthermore, SUA levels increased by the synergistic interaction of uACR with visceral adiposity and blood pressure, which may suggest obesity-related hypertension with altered renal hemodynamics as the primary mechanism. In the second part, we analyzed data captured in a representative population sample of French Canadians (CARTaGENE study) with more detailed urine biochemical analyses available. This study yielded two novel observations. First, we showed that the rs13129697 major T allele, which has been associated with increased SUA levels in our analysis as well as in prior publications, was associated with a paradoxical decrease in uACR. The reason for this discrepant finding is the...
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Contribution of particular vasoactive systems in the development of chronic kidney disease
Drábková, Natálie ; Vaněčková, Ivana (advisor) ; Vaňourková, Zdeňka (referee)
Chronic kidney disease (CKD) is a life-threating disease which arises as a frequent consequence of diabetes and hypertension. Since it is going on silently, CKD often progresses to the end-stage renal disease. It is therefore necessary to combat this disease especially due to the fact that the world population is growing old. The aim of this work was to determine the contribution of selected vasoactive systems contributing to the maintenance of high blood pressure in the developmental and established phase of CKD. Two models of CKD were used: 5/6 nephrectomy in Ren-2 transgenic rats (TGR) and stenosis of renal artery (2K1C) in Wistar rats. We demonstrated that renin-angiotensin system does not play so important role in blood pressure maintenance in both CKD models. By contrast, a more important role has sympathetic nervous system. During both the developmental and established phase of CKD, vasoconstrictor systems prevail above vasodilator NO-synthase effects. In fact, the role of NO-dependent vasodilation gradually decreased in nephrectomized TGR rats, while it was unchanged in Wistar rats with 2K1C hypertension.
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Genetic and molecular mechanisms of arterial hypertension in relation to chronic inflammation, oxidative stress, and chronic kidney disease
Krajčoviechová, Alena ; Cífková, Renata (advisor) ; Widimský, Jiří (referee) ; Vaněčková, Ivana (referee)
This thesis provides an appraisal of the structure of clustering of metabolic phenotypes and evaluates the pathophysiological mechanisms underlying the relationship between urinary uric acid and albumin excretion. Two population-based studies were involved. In the first part, we used data obtained in a large representative cross-sectional survey in the Czech Republic (Czech post-MONICA study). We showed that the urinary albumin/creatinine ratio (uACR) was an independent factor for an increase in serum uric acid (SUA) levels in adults without manifest metabolic syndrome (MetS), but with 1-2 MetS component(s). Furthermore, SUA levels increased by the synergistic interaction of uACR with visceral adiposity and blood pressure, which may suggest obesity-related hypertension with altered renal hemodynamics as the primary mechanism. In the second part, we analyzed data captured in a representative population sample of French Canadians (CARTaGENE study) with more detailed urine biochemical analyses available. This study yielded two novel observations. First, we showed that the rs13129697 major T allele, which has been associated with increased SUA levels in our analysis as well as in prior publications, was associated with a paradoxical decrease in uACR. The reason for this discrepant finding is the...
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The role of endothelin system in the treatment of chronic renal failure
Drábková, Natálie ; Vaněčková, Ivana (advisor) ; Vebr, Pavel (referee)
Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent consequence of diabetes and hypertension. Since it is silent for a long time, it often progresses to end-stage renal disease (ESRD). Managing chronic kidney disease, the prevalence of which is sharply increasing in the last decades due to the ageing of the world population, is thus major health problem. Apart from blockers of renin-angiotensin system, which are used as the "golden standard" in the treatment of CKD due to their antihypertensive and renoprotective effects, other strategies are also applied for the management of this disease. A relatively new class of therapeutics - blockers of endothelin system - seems to be very promising in this field.
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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra ; Neckář, Jan (advisor) ; Nováková, Olga (referee) ; Vaněčková, Ivana (referee)
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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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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název v anglickém jazyce není uveden
Böhmová, Radka ; Matl, Ivo (advisor) ; Třeška, Vladislav (referee) ; Vaněčková, Ivana (referee)
Background. TGF- is a key profibrogenic cytokine associated with chronic allograft nephropathy (CAN) pathogenesis. Renal ischemia/reperfusion (I/R) injury and hypertension represent important factors contributing to the development of CAN. The aim of the first, experimental part of the present study was to investigate the effect of immunosuppressant sirolimus in a model of accelerated renal injury in hypertensive transgenic rats (TGRs). The aim of the second, clinical part was to correlate the degree of CAN in the protocol biopsy of transplanted patiens with TGF-1 plasma levels and plasma levels of fibronectin. Another aim was to evaluate TGF-1 and fibronectin plasma levels in patients treated with different immunosuppressive (IS) regimes. Methods. Experiments were performed in TGR(mREN-2)-27 rats and their normotensive controls. We used a model of accelerated renal I/R injury. In clinical part of the present study, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 105 kidney transplant recipients treated with different IS regimes 12 months after renal transplantation. Conclusions. Hypertension induced by high levels of renin in transgenic rats aggravated the renal injury induced by I/R injury. Sirolimus treatment was shown...
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