It is not known how ACE inhibitor and angiotensin II receptor blocker (ARB) attenuate heart failure (HF) in viable ischemic hearts. To assess it, in a rat coronary stenosis (CS) model, we administered a vehicle, quinapril (Q), candesartan (C) or both orally for 12 weeks. Compared to the sham, the vehicle-group showed impaired myocardial perfusion, impaired coronary endothelial NO function in vitro, exhausted myocardial mitochondrial respiration, larger left ventricular (LV) dimensions and lower ejection fraction, lower LVdP/dt, lower slopes of LV end-systolic pressure-dimension relations (ESPDRs), and increased myocardial fibrosis. Treatment with Q or C ameliorated these parameters without modifying the epicardial CS severity. Moreover, their combination maintained similar myocardial perfusion despite a trend of lower blood pressure, and showed distinctive neurohumoral modulation, normalized mitochondrial respiration and increased ESPDR slopes. Thus, improved MBF and CFR by Q or C are the key to alleviate CS-induced HF, and their combination may have a therapeutic significance partly through ameliorated mitochondrial respiration and improved LV systolic function.