Nicorandil Attenuates Ischemia-Reperfusion Injury Via Inhibition of Norepinephrine Release From Cardiac Sympathetic Nerve Terminals

Abstract

SummaryA large amount of norepinephrine (NE) released from cardiac sympathetic nerve terminals might accelerate myocardial ischemic injury. Nicorandil (NICO), KATP channel opener, could attenuate cardiac NE release from the sympathetic nerve terminals during ischemia. The present study aimed to investigate the effects of NICOinduced attenuation of cardiac NE release on myocardial ischemia-reperfusion (I/R) injury in rats, by comparison with the effect of cardiac sympathetic denervation on I/R injury.Cardiac interstitial NE (iNE) concentrations were determined using a microdialysis method. Rats were divided into 3 groups; control, NICO, and denervation groups. Cardiac sympathetic denervation was performed by painting 10% phenol on the left ventricular epicardium 7 days before producing ischemia. The left coronary artery was ligated for 30 minutes and then re-perfused for 120 minutes. NICO (50 μg/kg/minute) was infused intravenously starting 20 minutes before the coronary occlusion to the end of the ligation.The infarct size of the left ventricle was smaller in rats treated with NICO than in control rats (20.2 ± 3.0 versus 50.6 ± 14.7%, P < 0.01). Sympathetic denervation also reduced infarct size (28.5 ± 10.4 %, P < 0.01), which was not significantly different from that in the NICO group. At the end of 30-minute ischemia, iNE increased markedly in control rats (0.1 ± 0.1 to 20.6 ± 5.3 10 3 pg/mL), whereas the increase was completely inhibited in denervated rats. NICO markedly attenuated the increase (4.9 ± 3.0 × 10 3 pg/mL, P < 0.01) during ischemia.NICO-induced attenuation of neural NE release during ischemia might, at least in part, contribute to myocardial protection against I/R injury. (Int Heart J 2017; 58: 787-793)

Increased Bioavailable Berberine Protects Against Myocardial Ischemia Reperfusion Injury Through Attenuation of NFκB and JNK Signaling Pathways

“…This is known as reperfusion injury. 15,16) Berberine (BBR) is an alkaloid derivative from the plant Berberis vulgaris (European barberry), which has been extensively studied for its multiple pharmacological activities. Our group and others have reported that BBR could attenuate heart injuries induced by ischemia reperfusion.…”

Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment

“…Our experimental results showed that MI injury significantly changes the characteristics of SCG neurons. Previous work has shown that MI causes an increased activity of sympathetic nerve and norepinephrine (NE) released from the sympathetic nerve endings in the myocardium ( Robador et al, 2012 ; Wu et al, 2012 ; Hall et al, 2016 ; Fukui et al, 2017 ). The probability of inducing continuous AP in SCG neurons was increased in MI groups.…”

“…The resulting effect is increased sympathetic activity ( Howard-Quijano et al, 2017 ). In the longer term, a large amount of norepinephrine (NE) is released from sympathetic nerves ( Wu et al, 2012 ; Fukui et al, 2017 ), potentially leading to cardiac arrhythmias. Thus, both cardiac and neuronal factors could modify the outcome ( Armour, 1999 ).…”

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