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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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