Dapagliflozin and exercise both improved systolic function and contractility in rats with exercise-induced hypertrophy, with dapagliflozin having no effect on hypertrophy size.
Does dapagliflozin combined with exercise training improve cardiac morphology and function in young male rats?
In a rat model, dapagliflozin and exercise training independently and additively improved systolic function and contractility without altering the exercise-induced hypertrophic response.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Regular exercise training has been described as a cardiovascular polypill. Sodium-glucose transport 2 inhibitor (SGLT2i) dapagliflozin (Dapa) evolved into one of the most favorable therapeutic option for the treatment of heart failure, independent from systolic function. The effect of SGLTi therapy on physiological hypertrophy, thus the interaction of exercise training and SGLT2i therapy has not yet been examined and might lead to mechanistic insight. Purpose We aimed to investigate the effect of Dapa treatment on the cardiac morphology and function in a rat model of exercise-induced myocardial hypertrophy. Methods We divided our young male rats into four groups: untrained, untreated controls (CoCo), exercised untreated (ExCo), untrained dapagliflozin-treated (CoDa) and exercised dapagliflozin-treated (ExDa) animals. Exercised animals underwent a 12-week-long swim training protocol and Dapa treatment was provided by daily galvage (1 mg/kgBW). Echocardiography and pressure-volume analysis was performed to characterize left ventricular (LV) morphological and functional alterations. Permeabilized cardiomycytes were used to investigate sarcomerdynamics parameters and troponin I (TnI) phosphorylation was determined by Western-blot. Results Post-mortem heart weight and echocardiography showed significant, similar degree of myocardial hypertrophy in both exercised groups (heart-weight CoCo:1.19±0.04g, ExCo: 1.43±0.05g, CoDa: 1.22±0.04g, ExDa: 1.45±0.05g). Both exercise training and Dapa treatment were associated with improved sytolic performance (stroke volume CoCo:136±28µl, ExCo: 172±23 µl, CoDa: 177±36µl, ExDa: 195±45µl) and active relaxation. The load-independent contractility parameters (ESPVR, PRSW) showed similar alterations: both Dapa and exercise treatment were related to a significant improvement along with improved maximal force of cardiomycytes. The co-treated ExDa group was associated with the most improved systolic parameters. Cardiomyocyte calcium (Ca)-sensitivity was improved only by exercise training. The overal phosphorylation of TnI was decreased by both interventions and co-treatment was associated with more pronounced hypophosphorylation. While Ser22/23 phosphorylation showed similar pattern to total TnI, Thr144 phosphorylation was decreased only by exercise training. Conclusions Dapagliflozin treatment did not influence the exercise-induced myocardial hypertrophic response. Both regular exercise and SGLT2i administration resulted in similar systolic and contractility improvement, that might be associated with Ser22/23 Troponin I phosphorylation. Ca-sensitivity was improved solely by exercise training and might be in relation with Thr144 hypophosphorylation.
Oláh et al. (Sat,) reported a other. Dapagliflozin and exercise both improved systolic function and contractility in rats with exercise-induced hypertrophy, with dapagliflozin having no effect on hypertrophy size.
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