Angiotensin-Converting Enzyme Inhibition After Experimental Myocardial Infarct

Abstract

We sought to define the contribution of each of the 2 kinin receptors (bradykinin 1 receptor [B ₁ R] and bradykinin 2 receptor [B ₂ R]) to the cardioprotection of angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarct. Wild-type mice and gene knockout mice missing either B ₁ R or B ₂ R 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 1 R ^−/− groups the FS was reduced by 24% and was no different (at 28%) with ACE inhibition; in the B ₂ R ^−/− 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 B ₁ R remained highly overexpressed in the B ₂ R ^−/− mice throughout, whereas the overexpressed B ₂ R became significantly suppressed in the B ₁ R ^−/− 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 B ₂ R as believed previously; but, whereas with potentiated bradykinin in the absence of B ₁ R, the upregulation of B ₂ R is simply insufficient to provide full cardioprotection, in the absence of B ₂ R, the upregulated B ₁ R actually seems to inflict further tissue damage.