Abstract—We sought to define the contribution of each of the 2 kinin receptors (bradykinin 1 receptor [B₁R] and bradykinin 2 receptor [B₂R]) to the cardioprotection of angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarct. Wild-type mice and gene knockout mice missing either B₁R or B₂R were submitted to coronary ligation with or without concurrent ACE inhibition and had evaluation of left ventricular systolic capacity by assessment of fractional shortening (FS). Baseline FS was similar in all of the animals and remained unchanged in sham-operated ones. At 3 weeks after myocardial infarct, in the wild-type group there was a 27% reduction of FS (P<0.5) without ACE inhibition and 8% with ACE inhibition; in the B₁R^-/- groups the FS was reduced by 24% and was no different (at 28%) with ACE inhibition; in the B₂R^-/- groups, however, the FS was decreased by 39% and with ACE inhibition was decreased further by 52%. Analysis of bradykinin receptor gene expression in hearts showed that when one receptor was missing, the other became significantly upregulated; but the B₁R remained highly overexpressed in the B₂R^-/- mice throughout, whereas the overexpressed B₂R became significantly suppressed in the B₁R^-/- mice in a manner quantitatively and directionally similar to that of wild-type mice. We conclude that both bradykinin receptors contribute to the cardioprotective bradykinin-mediated effect of ACE inhibition, not only the B₂R as believed previously; but, whereas with potentiated bradykinin in the absence of B₁R, the upregulation of B₂R is simply insufficient to provide full cardioprotection, in the absence of B₂R, the upregulated B₁R actually seems to inflict further tissue damage.