ESC Congress 2026 Abstract · Oct 26, 2026
Prophylactic dapagliflozin attenuates pulmonary vascular remodelling, preserves right ventricular function, and maintains exercise capacity in a monocrotaline-induced pulmonary hypertension rat model
By Asal S, Kilic S, Yavuz S et al.
Background: Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by vascular remodelling, elevated pulmonary vascular resistance, and right ventricular (RV) failure. Preventive strategies for at-risk populations remain absent. SGLT2 inhibitors confer pleiotropic cardioprotective benefits, yet their prophylactic potential in PAH is unexplored. We investigated whether dapagliflozin pretreatment attenuates MCT-induced pulmonary hypertension. Methods: Twenty-four male Sprague-Dawley rats were randomised to Control, MCT (60 mg/kg s.c., day 30), or MCT+DAPA (oral dapagliflozin 1.5 mg/kg/day × 30 days prior to MCT; n=8/group). Serial echocardiography (days 1, 30, 60), forced swimming (15 sessions), electrocardiography, terminal right atrial pressure (RAP), and histopathological quantification of pulmonary arteriolar medial wall thickness (MWT) were performed. Results: MCT induced profound RV dysfunction (TAPSE: 1.5±0.3 mm), pulmonary arterial dilatation (4.7±0.3 mm), abbreviated acceleration time (PAAT: 17.8±2.1 ms), RV dilatation (RVD 7.3±0.8 mm), elevated RAP (11.00±2.13 mmHg), and severe arteriolar MWT (59.2±6.9%), all p<0.001 vs. Control. Dapagliflozin pretreatment significantly attenuated each parameter: TAPSE 2.4±0.3 mm; PAAT 32.8±4.0 ms; PA diameter 3.4±0.3 mm; RAP 6.61±1.49 mmHg; MWT 32.1±3.4% (~46% reduction; all p<0.001 vs. MCT) (Figure 1). LV systolic function was preserved across all groups (LVEF p=0.328). Exercise capacity diverged markedly from session 10: MCT median 214 s vs. MCT+DAPA 1187 s vs. Control 2250 s at session 15 (p<0.001). MCT-induced ECG abnormalities (tachycardia, PR prolongation, QRS widening, QTc prolongation) were partially normalised by dapagliflozin. Representative Doppler images demonstrating preserved PAAT are shown in Figure 2. Conclusions: Prophylactic dapagliflozin comprehensively attenuated MCT-induced pulmonary hypertension, preserving RV function, reducing vascular remodelling, normalising electrophysiology, and maintaining exercise capacity. These findings support investigation of SGLT2 inhibitors as preventive agents in PAH.Figure-1For image description, please refer to the figure legend and surrounding text.Figure-2For image description, please refer to the figure legend and surrounding text.