BACKGROUND/AIMS: As a vasodilatory drug used to treat angina, nicorandil has been shown to induce an infarct-limiting effect in various experimental animal models of myocardial ischemia-reperfusion (IR). There are multiple mechanisms causing the IR injury, among which, the endoplasmic reticulum (ER) stress and ER stress-initiated apoptosis are implicated to play an important role. However, whether ER stress is involved in nicorandil-induced cardioprotection is unknown. METHODS: Post-ischemic functional recovery, lactate dehydrogenase (LDH) release and infarct size in perfused rat hearts subjected to global no-flow I/R were measured to analysis the effect of nicorandil and ER stress inducer of tunicamycin as well as phosphatidylinositol 3-kinase (PI3K) inhibitor of wortmannin on the I/R hearts. The I/R hearts tissue were harvested to evaluate apoptosis ratio with TUNEL assay and protein expression with western blot. RESULTS: We showed that nicorandil ameliorated postischemic contractile recovery, as well as significantly reduced myocardial infarct size at a dose-dependent manner. Furthermore, nicorandil treatment inhibited the IR-induced apoptosis and ER stress. The beneficial effects of nicorandil were blocked by ER stress inducer, tunicamycin and specific phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. CONCOLUSION: We conclude that the cardioprotection of nicorandil was at least in part mediated via inhibition of ER stress-induced apoptotic cell death through PI3K/Akt pathway.
BACKGROUND/AIMS: As a vasodilatory drug used to treat angina, nicorandil has been shown to induce an infarct-limiting effect in various experimental animal models of myocardial ischemia-reperfusion (IR). There are multiple mechanisms causing the IR injury, among which, the endoplasmic reticulum (ER) stress and ER stress-initiated apoptosis are implicated to play an important role. However, whether ER stress is involved in nicorandil-induced cardioprotection is unknown. METHODS: Post-ischemic functional recovery, lactate dehydrogenase (LDH) release and infarct size in perfused rat hearts subjected to global no-flow I/R were measured to analysis the effect of nicorandil and ER stress inducer of tunicamycin as well as phosphatidylinositol 3-kinase (PI3K) inhibitor of wortmannin on the I/R hearts. The I/R hearts tissue were harvested to evaluate apoptosis ratio with TUNEL assay and protein expression with western blot. RESULTS: We showed that nicorandil ameliorated postischemic contractile recovery, as well as significantly reduced myocardial infarct size at a dose-dependent manner. Furthermore, nicorandil treatment inhibited the IR-induced apoptosis and ER stress. The beneficial effects of nicorandil were blocked by ER stress inducer, tunicamycin and specific phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. CONCOLUSION: We conclude that the cardioprotection of nicorandil was at least in part mediated via inhibition of ER stress-induced apoptotic cell death through PI3K/Akt pathway.
Authors: Rachel T Sullivan; Ngoc T Lam; Margaret Haberman; Margaret J Beatka; Muhammad Z Afzal; Michael W Lawlor; Jennifer L Strande Journal: BMC Cardiovasc Disord Date: 2021-06-15 Impact factor: 2.298