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.

Duka A, Kintsurashvili E, Duka I, Ona D, Hopkins TA, Bader M, Gavras I, Gavras H.

Hypertension and Atherosclerosis Section, Department of Medicine, and Cardiovascular Institute, Boston University School of Medicine, Mass; Max Delbrk Center for Molecular Medicine, Berlin, Germany.