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 degree 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 microM) 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.