Nicorandil Suppresses Ischemia-Induced Norepinephrine Release and Ventricular Arrhythmias in Hypertrophic Hearts.

Miyuki Kobara, Toshihiro Amano, Hiroe Toba, Tetsuo Nakata

Cardiovascular drugs and therapy 2023 Feb

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Ventricular arrhythmias (VAs) are a common cause of sudden death in acute myocardial infarction (MI), for which hypertension is a major risk factor. Nicorandil opens ATP-sensitive potassium (KATP) channels, which are expressed by nerve terminals and cardiomyocytes and regulate the release of norepinephrine (NE). However, the effects of nicorandil on ischemic NE release in cardiac tissue remain unclear. Therefore, we herein investigated whether nicorandil suppressed interstitial NE concentrations and VAs during acute MI in pressure overload-induced hypertrophic hearts. Rats were divided into two groups: an abdominal aortic constriction (AAC) group and sham-operated (Sham) group. Four weeks after constriction, cardiac geometry and functions were examined using echocardiography and hemodynamic analyses. Myocardial ischemia was induced by coronary artery occlusion for 100 min with or without the administration of nicorandil. VAs were assessed by electrocardiography, and NE concentrations in the ischemic region were measured using a micro-dialysis method. AAC induced left ventricular hypertrophy with diastolic dysfunction. VAs markedly increased in the early phase (0-20 min) of ischemia in both groups and were more frequent in the AAC group. Cardiac interstitial NE concentrations were higher in the AAC group before ischemia and significantly increased during ischemia in both groups. Nicorandil significantly suppressed ischemia-induced VAs and NE increases in the AAC group. Ischemia-induced VAs were more frequent in hypertrophic hearts and associated with high interstitial concentrations of NE. The attenuation of ischemia-induced increases in NE through neuronal KATP opening by nicorandil may suppress ischemia-induced VAs in hypertrophic hearts. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Miyuki Kobara, Toshihiro Amano, Hiroe Toba, Tetsuo Nakata. Nicorandil Suppresses Ischemia-Induced Norepinephrine Release and Ventricular Arrhythmias in Hypertrophic Hearts. Cardiovascular drugs and therapy. 2023 Feb;37(1):53-62