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Neuromodulation in heart failure
Naar, Jan ; Ošťádal, Petr (advisor) ; Rokyta, Richard (referee) ; Vízek, Martin (referee)
The prognosis of heart failure with reduced ejection fraction remains poor. Neurohumoral activation, including increased cardiac sympathetic nerve activity, plays an important role in the pathogenesis as well as disease progression. Recently, several neuromodulation strategies have been proposed that aim to directly affect the residual autonomic imbalance. Spinal cord stimulation is one of the proposed methods. In the clinical part of this project, we assessed the mid-term effect of spinal cord stimulation on cardiac sympathetic nerve activity and the acute effect on autonomic balance. In the total study population, we did not detect any changes in cardiac sympathetic nerve activity or heart rate variability. However, we observed that the patients with high baseline sympathetic nerve activity or low heart rate variability responded favourably to therapy, reflected in reduced cardiac sympathetic nerve activity and increased heart rate variability. Considering these results, we conducted an experimental study focused on the effect of acute severe heart failure on heart rate variability. In a porcine model of hypoxic myocardial dysfunction, we observed a significant reduction in heart rate variability in all parameters recorded. Our results indicate that spinal cord stimulation may improve autonomic...
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Neural mechanisms in the pathogenesis of spontaneous hypertension in the rat
Vavřínová, Anna ; Zicha, Josef (advisor) ; Haluzík, Martin (referee) ; Neckář, Jan (referee)
Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and 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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Neural mechanisms in the pathogenesis of spontaneous hypertension in the rat
Vavřínová, Anna ; Zicha, Josef (advisor) ; Haluzík, Martin (referee) ; Neckář, Jan (referee)
Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and 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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The role of Rho-kinase signaling pathway in the regulation of blood pressure
Brunová, Aneta ; Zicha, Josef (advisor) ; Kopkan, Libor (referee)
Calcium sensitization represents a mechanism that enables vascular smooth muscle cells to change the sensitivity of the contractile apparatus to intracellular calcium The aim of this study was to determine to what extent is calcium sensitization modulated by the renin- angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids produced by cyclooxygenase (COX). For this purpose we studied the effects of acute and chronic blockade of particular systems on blood pressure changes elicited in conscious normotensive rats by administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used in all experiments. Main findings of this study are as follow: 1) Decrease of blood pressure elicited by Rho-kinase inhibition was enhanced under the conditions of acute NOS inhibition. Inhibition of NOS was shown to have a bigger effect than COX inhibition (this was confirmed under the conditions of acute RAS and SNS inhibition as well). These findings are in agreement with the hypothesis that NO exerts a suppressive effect on calcium sensitization. 2) Chronic NOS inhibition caused hypertension characterized by a more pronounced blood pressure lowering after Rho-kinase inhibition in comparison with control. NO chronically suppresses the calcium...
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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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