Effect of Sildenafil on Sympathetic Hyperinnervation in Post-infarcted Rat Hearts

Tsung-Ming Lee, Nen-Chung Chang

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72 Citations (Scopus)


Sildenafil has been shown to provide cardioprotection against ischemia/reperfusion injury via activation of mitochondrial ATP-sensitive potassium (KATP) channels. We assessed whether sildenafil attenuates cardiac sympathetic innervation after myocardial infarction through activation of KATP channels. After ligation of the anterior descending artery, male Wistar rats were randomized to either vehicle, nicorandil, pinacidil, sildenafil, glibenclamide, or a combination of nicorandil and glibenclamide, pinacidil and glibenclamide or sildenafil and glibenclamide for 4 weeks. To elucidate the role of mitochondrial KATP channels in modulating nerve growth factor, 5-hydroxydecanoate was assessed in an in vitro model. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats at the remote zone compared with sham. Immunohistochemical analysis for tyrosine hydroxylase, growth associated factor 43 and neurofilament also confirmed the change of myocardial norepinephrine. This was paralleled by a significant upregulation of nerve growth factor protein expression and mRNA in the vehicle-treated rats, which reduced after administering either nicorandil, pinacidil or sildenafil. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those treated with sildenafil. In contrast, beneficial effects of sildenafil were reversed by the addition of either glibenclamide or 5-hydroxydecanoate. Chronic use of sildenafil after infarction, resulting in attenuated sympathetic innervation by activation of mitochondrial KATP channels, may modify the arrhythmogenic response to programmed electrical stimulation.
Original languageEnglish
Pages (from-to)787.8-787.8
JournalFASEB Journal
Issue number1 Supplement
Publication statusPublished - Apr 1 2010


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