The principal findings of the current study are that (1) infusion of angiotensin II at a dose of 600 ng/kg/min combined with 1% NaCl in the drinking water constitutes a model of hypertension-associated HFpEF characterized by cardiac hypertrophy, capillary rarefaction, prominent interstitial fibrosis and perivascular fibrosis, oxidative stress, pronounced cardiac dysfunction, and pulmonary congestion; (2) treatment with apo A-IMilano nanoparticles reverses oxidative stress, capillary rarefaction, perivascular fibrosis, cardiac dysfunction, and heart failure. Here, AGT is linked to hypertensive disorder.