The protective effect of Na+/Ca2+ exchange blocker kb-r7943 on myocardial ischemia-reperfusion injury in hypercholesterolemic rat.
KB-R7943 reduces lethal reperfusion injury under normal conditions, but its effectiveness under certain pathological states is in dispute. In the present study, we sought to determine the effect of KB-R7943 in hyperlipidemic animals and assess if the K ATP (+) are involved in the protective mechanisms. In group 1 (G1), isolated rat hearts underwent 25 min global ischemia (GI) and 120 min reperfusion (R). In group 2 (G2), G1 was repeated but the animals were subjected to a 1.5 % cholesterol-enriched diet during 6 weeks (hypercholesterolemic animals). In group 3 (G3), G2 was repeated but 1 μM KB-R7943 was added to the perfusate for 10 min from the start of reperfusion. In group 4 (G4), G3 was repeated, and glibenclamide (K ATP (+) , blocker, 0.3 μM) was administered. The infarct size was measured by triphenyltetrazolium. The infarct size was 35 ± 5.0 % in G1 and 46 ± 8.7 % in G2 (P < 0.05); KB-R7943 reduced the infarct size (28.6 ± 3.3 % in G3 vs. G2, P < 0.05). In addition, KB-R7943 attenuated apoptotic cell (G3 vs. G2, P < 0.05), but glibenclamide abolished the effect reached by KB-R7943. Thus, diet-induced hypercholesterolemia enhances myocardial injury; KB-R7943 reduces infarct size and apoptosis in hyperlipidemic animals through the activation of K(+)ATP channels.
Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Yongkui
Y
Ren
Liju
L
Deng
Yunfei
Y
Cai
Yan
Y
Lv
Dalin
D
Jia
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006937:Hypercholesterolemia / Q000150:complications*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D054086:KATP Channels; D019831:Sodium-Calcium Exchanger; D013890:Thiourea