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Pharmacological possibilities for amending renal dysfunction in experimental model of heart failure
Krátký, Vojtěch ; Charvátová, Zuzana (advisor) ; Bednářová, Vladimíra (referee) ; Melenovský, Vojtěch (referee)
Mechanisms underlying the development of renal dysfunction and pharmacological possibilities for its amending in patients with chronic heart failure are still incompletely understood. The aim of the study was thus to compare the effect of treatment with an ACE inhibitor (ACEi), AT1 receptor blocker (ARB) or combined angiotensin receptor-neprilysin inhibitor (ARNi) on renal hemodynamic and excretory functions in experimental models of heart failure induced by placing an aorto-caval fistula (ACF) in combination with hypertension or preexisting renal disease. In normotensive and especially in hypertensive rats with high- output heart failure 20 weeks after ACF placement, ARB administration, dissimilarly to an ACEi treatment, was shown to prevent renal hypoperfusion and hypoxia. In addition, heart failure rats treated with ARB exhibited lower ROS generation, improved renal NO bioavailability, and normal renal SNS activity. The failure of ACEi to ameliorate renal hypoperfusion in rats with heart failure may be a consequence of insufficiently suppressed intrarenal RAS along with enhanced renal SNS activity in the face of depleted compensatory mechanisms, namely NO. Combined ARNi treatment in rats with induced heart failure superimposed on progressive renal dysfunction significantly improved survival...
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Aldosterone synthase in arterial hypertension and possible influence of its genenetic polymorphism on left ventricular hypertrophy
Heller, Samuel ; Horký, Karel (advisor) ; Málková, Jana (referee) ; Widimský, Jiří (referee)
Part I. The aldosterone synthase gene (CYP11B2) polymorphism T-344C in blood pressure and left ventricular hypertrophy. BACKGROUND: Aldosterone is a key cardovascular hormone, it significantly influences volume, pressure and electrolyte balance. Aldosterone plays an important role in development of left ventricular (LV) hypertrophy and myocardial fibrosis. The aldosterone synthase gene (CYP11B2) is an important candidate gene region in essential hypertension. DESIGN AND METHODS: We assessed the influence of the T-344C polymorphism of aldosterone synthase - the rate-limiting enzyme in aldosterone biosynthesis - on the structure of the left ventricle in young normotensive men. The population included 113 normotensive mid-European Caucasian men aged 18-40 years (mean 27 +/- 5 years). We also studied the association of -344T/C polymorphism of the CYP11B2 gene with the presence and severity of hypertension in 369 individuals, of whom 213 were hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive) and 156 were healthy normotensive subjects. The genotype was assessed using polymerase chain reaction with subsequent cleavage with restriction enzyme HAEIII (restriction fragment length polymorphism method) and visualization with ethidium bromide. Plasma renin activity (PRA) and plasma...
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