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Pathophysiological mechanisms of chronic kidney disease progression
Sedláková, Lenka ; Kopkan, Libor (advisor) ; Švandová, Ivana (referee)
The kidneys are an essential organ that maintains the homeostasis of body fluid and ions, it filters metabolites and plays important endocrine role. Renal function is controled by many mechanisms with a close interaction that can work independently without central control. These mechanisms are regulated by both systemic and intrarenal humoral systems and their physiological balance sustains the optimal kidney fuction. Any disturbance of this balance leads to the impairments of renal function and progression of renal injury and thus the kidney works inappropriately. The renal insufficiency and diseases remain significant problem despite modern medicine. This is results of several risk factors such as age, genetic predisposition and low birth weight, increase of civilization diseases - diabetes, hypertension, autoimmune disorders, but also bad habits such as unhealthy lifestyle, smoking etc. These factors can lead to the acute or chronic kidney diseases often without known cause. Than the question is an early diagnosis and optimal treatment to preserve kidney function and stop the progression of terminal renal damage. This thesis should show the importance of kidney function and outline problems and consequences of renal insufficiency particularly during chronic kidney disease. Keywords: Renal...
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Effect of combined endothelin and renin-angiotensin systems blockade on blood pressure and chronic kidney disease regression in model of angiotensin II-dependent hypertension
Sedláková, Lenka ; Kopkan, Libor (advisor) ; Bürgelová, Marcela (referee)
and key words Enhanced activation of renin-angiotensin system (RAS) and endothelin system (ES) plays the key pathophysiological role in the progression of hypertension and the chronic kidney disease (CKD). The aim of this study was to verify wheter the combined inhibition RAS and selective inhibition ETA receptor for endothelin 1 (ET-1) will show additive renoprotective effects in experimental model CKD. This therapeutic aproach was tested on the transgenic rats with mouse renin gen (TGR), to whome ablation nephrectomy (5/6 NX) was done in the age of 6 weeks. After next 6 weeks the relevant treatment was given in drinking-water: dual RAS blockade (trandolapril 6mg/L + losartan 100mg/L) or the combination of dual RAS blockade + inhibitor of ETA receptor (atrasentan 25mg/L). Results of the first series show 100 % mortality in untreated rats with 5/6 NX to the 30th week. Both type of treatments increased the survival rate up to 30 % in 5/6 NX TGR after the 50th week. In the second series influence of treatments on the blood pressure (BP) was monitored in 5/6 NX TGR, which had systolic BP over 210 mmHg. Both treatments decreased BP to the level normotensive rats and reduced heart hypertrophy. In the third series the results showed that treatment significantly decreased renal level of angiotensin II...
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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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Pathophysiological mechanisms of chronic kidney disease progression
Sedláková, Lenka ; Kopkan, Libor (advisor) ; Švandová, Ivana (referee)
The kidneys are an essential organ that maintains the homeostasis of body fluid and ions, it filters metabolites and plays important endocrine role. Renal function is controled by many mechanisms with a close interaction that can work independently without central control. These mechanisms are regulated by both systemic and intrarenal humoral systems and their physiological balance sustains the optimal kidney fuction. Any disturbance of this balance leads to the impairments of renal function and progression of renal injury and thus the kidney works inappropriately. The renal insufficiency and diseases remain significant problem despite modern medicine. This is results of several risk factors such as age, genetic predisposition and low birth weight, increase of civilization diseases - diabetes, hypertension, autoimmune disorders, but also bad habits such as unhealthy lifestyle, smoking etc. These factors can lead to the acute or chronic kidney diseases often without known cause. Than the question is an early diagnosis and optimal treatment to preserve kidney function and stop the progression of terminal renal damage. This thesis should show the importance of kidney function and outline problems and consequences of renal insufficiency particularly during chronic kidney disease. Keywords: Renal...
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