Mineralocorticoid receptor (MR) antagonists slow down the progression of heart 
failure after myocardial infarction (MI), but the cell-specific role of MR in 
these benefits is unclear. In this study, the role of MR expressed in vascular 
smooth muscle cells (VSMCs) was investigated. Two months after coronary artery 
ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice 
treated with the MR antagonist finerenone (MI-fine) had improved left 
ventricular compliance and elastance when compared with infarcted control mice 
(MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary 
reserve assessed by magnetic resonance imaging was preserved (difference in 
myocardial perfusion before and after induction of vasodilatation, mL mg(-1) 
min(-1): MI-CTL: 1.1 ± 0.5, nonsignificant; MI-MR(SMKO): 4.6 ± 1.6 [P<0.05]; 
MI-fine: 3.6 ± 0.7 [P<0.01]). The endothelial function, tested on isolated 
septal coronary arteries by analyzing the acetylcholine-induced nitric 
oxide-dependent relaxation, was also improved by MR deletion in VSMCs or by 
finerenone treatment (relaxation %: MI-CTL: 36 ± 5, MI-MR(SMKO): 54 ± 3, and 
MI-fine: 76 ± 4; P<0.05). Such impairment of the coronary endothelial function 
on MI involved an oxidative stress that was reduced when MR was deleted in VSMCs 
or by finerenone treatment. Moreover, short-term incubation of coronary arteries 
isolated from noninfarcted animals with low-dose angiotensin-II (10(-9) mol/L) 
induced oxidative stress and impaired acetylcholine-induced relaxation in CTL 
but neither in MR(SMKO) nor in mice pretreated with finerenone. In conclusion, 
deletion of MR in VSMCs improved left ventricular dysfunction after MI, likely 
through maintenance of the coronary reserve and improvement of coronary 
endothelial function. MR blockage by finerenone had similar effects.