Abstract：
:It is a consensus view that a strategy to increase heart resistance to ischaemia-reperfusion is a warranted. Here, based on our previous study, we have hypothesized that a nicotinamide-rich diet could increase myocardial resistance to ischaemia-reperfusion. Therefore, the purpose of this study was to determine whether nicotinamide-rich diet would increase heart resistance to ischaemia-reperfusion and what is the underlying mechanism. Experiments have been done on mice on control and nicotinamide-rich diet (mice were a week on nicotinamide-rich diet) as well as on transgenic mice overexpressing SUR2A (SUR2A mice), a regulatory subunit of cardioprotective ATP-sensitive K(+) (K(ATP)) channels and their littermate controls (WT). The levels of mRNA in heart tissue were measured by real-time RT-PCR, whole heart and single cell resistance to ischaemia-reperfusion and severe hypoxia was measured by TTC staining and laser confocal microscopy, respectively. Nicotinamide-rich diet significantly decreased the size of myocardial infarction induced by ischaemia-reperfusion (from 42.5+/-4.6% of the area at risk zone in mice on control diet to 26.8+/-1.8% in mice on nicotinamide-rich diet, n=6-12, P=0.031). The cardioprotective effect of nicotinamide-rich diet was associated with 11.46+/-1.22 times (n=6) increased mRNA levels of SUR2A in the heart. HMR1098, a selective inhibitor of the sarcolemmal K(ATP) channels opening, abolished cardioprotection afforded by nicotinamide-rich diet. Transgenic mice with a sole increase in SUR2A expression had also increased cardiac resistance to ischaemia-reperfusion. We conclude that nicotinamide-rich diet up-regulate SUR2A and increases heart resistance to ischaemia-reperfusion.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Sukhodub A,Du Q,Jovanović S,Jovanović Adoi
10.1016/j.phrs.2010.01.008subject
Has Abstractpub_date
2010-06-01 00:00:00pages
564-70issue
6eissn
1043-6618issn
1096-1186pii
S1043-6618(10)00022-8journal_volume
61pub_type
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