Bradykinin metabolism in the isolated perfused rabbit heart

Background Bradykinin is a potent cardioprotective hormone, the beneficial role of which in vivo appears to be limited by its rapid metabolism. Inhibi tors of peptidases that degrade endogenously formed bradykinin are themselv es cardioprotective, presumably by increasing local bradykinin concentratio ns. As bradykinin-degrading peptidases are potential therapeutic targets, i t is important to identify these enzymes in different animal models of card iac function. Objective To determine the mechanism of bradykifiin degradation in the coro nary circulation of the rabbit, using an isolated perfused heart preparatio n. Design and methods [H-3]Bradykinin (16 nmol/l) was perfused as a bolus thro ugh the isolated rabbit heart in the presence and absence of specific pepti dase inhibitors, The effluent was collected and the radiolabeled metabolite s of [H-3]bradykinin were separated by high performance liquid chromatograp hy, identified, and quantified. Results [H-3]Bradykinin was metabolized to the extent of 62 +/- 3% in a sin gle passage through the rabbit coronary circulation at a physiological flow rate. The metabolites were identified as [H-3]bradykinin((1-5)) and [H-3]b radykinin((1-7)),accounting for 50 +/- 4 and 12 +/- 2% of the radioactivity , respectively. Co-perfusion with the angiotensin converting enzyme inhibit or, ramiprilat, completely blocked formation of these metabolites. Conclusions Angiotensin-converting enzyme fully accounts for the metabolism of [H-3]bradykinin in the rabbit coronary circulation. This result contras ts with data obtained using rat heart, which demonstrated a prominent role for aminopeptidase P in bradykinin metabolism in this species. (C) 2001 Lip pincott Williams & Wilkins.