Abstract

Arterial hypertension is a well-known risk factor for cardiac arrhythmias, while certain antihypertensive agents may also create conditions for arrhythmia occurrence. The aim of this study was to evaluate the effects of selected class III antiarrhythmic drugs on cardiac function and structure, as well as on oxidative stress status, in spontaneously hypertensive rats (SHRs). Male SHRs were treated for 4 weeks with dronedarone, amiodarone, or dofetilide. Cardiac function was assessed in vivo by echocardiography and ex vivo using the Langendorff model. Oxidative stress markers, myocardial morphology, and HSP70 and SERCA2 expression were analyzed. All drugs partially improved cardiac function in vivo, with dronedarone exerting the strongest antihypertensive effect. Ex vivo, dofetilide enhanced contractility and dronedarone reduced cardiac performance, whereas amiodarone showed intermediate effects. Oxidative stress was differentially modulated, with dofetilide and amiodarone improving antioxidant defenses, while dronedarone showed heterogeneous effects. Histologically, dofetilide preserved myocardial architecture most effectively, while amiodarone and dronedarone partially attenuated hypertensive remodeling. Treatments decreased HSP70 expression, while increasing SERCA2 expression, particularly in the dofetilide group. Class III antiarrhythmic drugs differentially affect cardiac function, redox balance, calcium handling, and myocardial remodeling in hypertension, which may contribute to their distinct antiarrhythmic and cardioprotective properties.

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