Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction

Figures

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  Figure 1. Time Course for Systolic Blood Pressure Time course for systolic blood pressure. n = 16 and 15 in deoxycorticosterone acetate (DOCA) control and empagliflozin (empa) groups, respectively. n = 7 to 8 in uninephrectomy (UNX) control and UNX empa groups. *p < 0.05 versus UNX + vehicle.

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  Figure 2. Representative Echocardiograms Representative echocardiograms (M-MODE) in (A) UNX + control, (B) UNX + empagliflozin, and (C) UNX + DOCA + control, and (D) UNX + DOCA + empa. Both left ventricular internal diameter systole (LVIDs) and wall thickness were reduced by empa in DOCA salt rats. *p < 0.05 versus UNX treated with vehicle. LVIDd = left ventricular internal diameter diastole; other abbreviations as Figure 1.

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  Figure 3. Steady-State Pressure−Volume Loops Empa-treated UNX + DOCA salt animals display a leftward shift with a reduction in end-diastolic volume (blue curve) compared with the UNX + DOCA salt control animals (gray curve). Abbreviations as in Figures 1 and 2.

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  Figure 4. Stained Sections (A to D) Representative hematoxylin and eosin and (E to H) picrosirius red stained sections. Hearts of UNX + DOCA salt rats showed evidence of (I) myocyte hypertrophy, together with both (J and K) perivascular and interstitial fibrosis. Empa reduced cardiomyocyte size in UNX + DOCA animals but had no effect on either interstitial or perivascular fibrosis. n = 7 to 8 in UNX control and UNX empa groups; n = 16 and 15 in DOCA control and empa groups, respectively. *p < 0.05 treated with UNX + control. †p < 0.05 treated with UNX + DOCA + control. CSA = cross-sectional area; other abbreviations as in Figure 1.

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  Figure 5. Heart Collagen 1 and III, ANP mRNA Levels Hearts of DOCA salt rats showed evidence of atrial natriuretic peptide (ANP) activation, together with increased collagen I (Col I) and III mRNA. Empa had no effect on either ANP, or Col I or III mRNA. n = 8 for control (Cont) UNX; n = 7 for UNX empa; n = 14 for control DOCA; n = 13 for empa DOCA. *p < 0.05 compared to UNX animals treated with UNX + control. RPL13a = ribosomal protein L13A housekeeping gene; other abbreviations as in Figure 1.