Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits.
Nicorandil has been shown to induce an infarct-limiting effect similar to that induced by the early phase of ischemic preconditioning (PC). The goals of this study were to determine whether nicorandil induces a delayed cardioprotection that is analogous to the late phase of ischemic PC and, if so, whether nicorandil-induced late PC is associated with upregulation of cardioprotective proteins. Chronically instrumented, conscious rabbits received vehicle (intravenous normal saline; control group, n = 10), nicorandil (100 microg/kg bolus + 30 microg x kg(-1) x min(-1) i.v. for 60 min; nicorandil group, n = 10), or ischemic PC (6 cycles of 4-min coronary occlusion/4-min reperfusion; PC group, n = 8). Twenty-four hours later, rabbits underwent a 30-min coronary occlusion, followed by 3 days of reperfusion. Myocardial infarct size was significantly reduced in rabbits pretreated with nicorandil (27.5 +/- 5.3% of the risk region) or with ischemia (30.3 +/- 4.2%) versus controls (59.1 +/- 4.7%, P < 0.05 vs. both). Furthermore, the expression of cyclooxygenase-2 (COX-2) and Bcl-2 was significantly elevated (+38% and +126%, respectively; P < 0.05) in myocardium of rabbits given nicorandil 24 h earlier versus controls. We conclude that nicorandil induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by upregulating COX-2 and Bcl-2.
Tang
Xian-Liang
XL
Institute of Moleculat Cardiology, University of Louisville, Louisville, KY 40292, USA.
Xuan
Yu-Ting
YT
Zhu
Yanqing
Y
Shirk
Gregg
G
Bolli
Roberto
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020108:Nicorandil / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011817:Rabbits
D000959:Antihypertensive Agents; D007527:Isoenzymes; D020108:Nicorandil; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases