Fig 2: Hemodynamic characteristics of the heart and BNP augmentation during 6 weeks of MCT treatment. (A) The RVSP and (B) RVEDP significantly increased in rats with MCT-induced pulmonary arterial hypertension. (C and D) RV function was enhanced, as confirmed by the increase in the +dP/dtmax and decrease in the -dP/dtmin. (E) The cardiac inotropic LVSP, (F) lusitropic LVEDP, (G) +dP/dtmax in the LV, (H) -dP/dtmin in the LV and (I) chronotropic HR in rats in the presence of MCT were evaluated by catheterization. (J) A significant increase in the level of plasma BNP due to the persistent pressure overload was revealed in MCT-treated rats. Values are expressed as the mean ± standard deviation (n=10). *P<0.05 and **P<0.01 vs. the CON group. MCT, monocrotaline; CON, control; RVSP/LVSP, right/left ventricular systolic pressure; RVEDP, right ventricular end-diastolic pressure; +dP/dtmax, maximal rate of ventricular pressure; -dP/dtmin, minimal rate of ventricular pressure; HR, heart rate; BNP, brain natriuretic peptide.

Fig 3: Effect of CANA on cardiac function. (A) Evaluation of the ratio of peak E to peak A (E/A) by echocardiography; (B) Left ventricular ejection fraction (EF); (C) Concentration of BNP in the serum; (D) Left ventricular anterior wall end diastole (LVAWd); (E) Left ventricular internal diameter end diastole (LVIDd); (F) Left ventricular mass AW; (G) Heart-to-body weight ratio (HW/BW); (H) Left ventricular anterior wall end systole (LVAWs); (I) Left ventricular internal diameter end systole (LVIDs); (J) Left ventricular posterior wall end systole (LVPWs); (K) Left ventricular posterior wall end diastole (LVPWd); (L) Fractional shortening (FS); CANA, canagliflozin; NSD, normal-salt diet; HSD, high-salt diet. ** p < 0.01 vs. NSD. # p < 0.05, ## p < 0.01 vs. HSD.

Fig 4: DIZE improved cardiac contractility and reduced plasma BNP and TNI levels. Comparison of LVSP (a), +dp/dtmax (b), and -dp/dtmax (c), as well as plasma concentrations of TnI (d) and BNP (e) in the sham, CLP, and CLP + DIZE treatment groups (n = 6 rats/group). * P < 0.05 vs sham group, ** P < 0.01 vs sham group; # P < 0.05 vs CLP group, ## P < 0.01 vs CLP group. Abbreviations: CLP, cecal ligation and puncture; DIZE, diminazene aceturate; LVSP, left ventricular systolic pressure; +dp/dtmax, maximal left ventricular pressure rising rate; -dp/dtmax, maximal left ventricular pressure declining rate; TnI, troponin I; BNP, brain natriuretic peptide

Fig 5: Administration of DAPA attenuates cardiac remodeling and improves cardiac dysfunction induced by Ang II in rats. A, B Analysis of ELISA of plasma ANP, BNP and Ang II levels; C HW, LVW, HW/TL ratios and HW/TL ratios; D representative examples of M-mode echocardiography images; E representative examples of left ventricular four-chamber 2Dspeckle tracking echocardiography imaging. Data are expressed as the mean ± SD (n = 6 rats per group). *P < 0.05 relative to CTL group. †P < 0.05 relative to Ang II group