Enalaprilat, an angiotensin-converting enzyme inhibitor, enhances functional preservation during long term cardiac preservation. Possible involvement of bradykinin and PKC

We investigated the effect of enalaprilat (ET) on long-term preservation of cardiac explant. Isolated rat hearts (n=7/group) were pretreated with 0 to 40 nM ET and stored at 0 degrees C for 16 h, Functional viability was assessed after 30-min working reperfusion without ET. Prestorage control function (mean+/-S.E.M.) (n=7) included heart rate (HR), 291+/-12 bpm; aortic flow (AF), 49.8+/-1.9 ml/min; coronary flow (CF), 25.2+/-1.3 ml/min; cardiac output (CO), 75.0+/-1.2 ml/min; and work, 89.4+/-4.7 g-m/min. Post-storage function of untreated hearts was: AF, 61%; CF, 43%; CO, 55%; work, 48% of control, ET (20 nM) enhanced AF recovery to 85%; CF, 58%; CO, 76%; work, 73% of control (P<0.05 v untreated), Hoe 140 (D-Arg-[Hyp2, Thi5,8, D-Phe7]BK) (1 nM), a bradykinin receptor antagonist, inhibited ET effect; function returned to the untreated level. Protein kinase C (PKC) inhibitors staurosporine (15 nM) and bisindolylmaleimide I (0.5 mu M) also blocked ET effect, After 4 h of cold storage, membrane PKC activity changed little from the prestorage level in the untreated hearts, but was elevated significantly from 52.8+/-5.2 pmol/min/mg to 74.7+/-8.2 by 20 nM ET (P<0.05 v untreated). Cytosol PKC did not change during 4 h cold storage with or without ET, Neither end-storage nor end-reperfusion myocardial ATP content was affected by 20 nM ET treatment. In conclusion, ET improves cardiac preservation possibly via bradykinin receptor and PKC without affecting ATP metabolism. (C) 1996 Academic Press Limited.