This study explored the association of cardioprotective role of thyroid hormones (TH) and benefit effects of grape juice (GJ) on vascular function against the apoptosis and inflammation associated with monocrotaline (MCT)-induced pulmonary hypertension (PH). Wistar rats were distributed into five groups: control; PH (MCT 60mg/kg i.p.); PH+GJ (GJ-7 µL/g / day, gavage for 14 days); PH+TH (T3, 2μg/100g/day, and T4, 8μg/100g/day, by gavage for 14 days); and PH+TH+GJ. Echocardiographic, morphometric measurements and expression of proteins associated with apoptosis and inflammation were evaluated. The reduced cardiac output (35%) in PH was attenuated in the PH+GJ, PH+TH, and PH+TH+GJ groups (P<0.05). Both GJ and TH had no effect on the PH-induced hypertrophy index. The PH + TH group showed reduced BAX (~90%) and increased Bcl2 levels (~80%) as compared to PH group (P<0.05). The PH-induced increase in caspase 3 was diminished (~92%) in the PH+TH (P<0.05). Both GJ and TH, isolated and combined, reduced caspase 9 levels (~70%). PH-provoked elevated NLRP3 levels was decreased (~90%) in PH+TH (P<0.05). The therapeutic approach showed cardioprotective effects in the PH model which may be mediated by mitigation of apoptosis and inflammation.