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.
Yang
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X
Department of Surgery, University of Rochester, NY 14642, USA.
Zhu
Q
Q
Fong
J
J
Gu
X
X
Hicks
G L
GL
Bishop
S P
SP
Wang
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015773:Enalaprilat / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009926:Organ Preservation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D015773:Enalaprilat; D001920:Bradykinin