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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/H3617    most recent 00875.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Lee, T.-M. Articles by Chang, N.-C. Search for Related Content PubMed PubMed Citation Articles by Lee, T.-M. Articles by Chang, N.-C.

Effect of pravastatin on sympathetic reinnervation in postinfarcted rats

¹Cardiology Section, Department of Medicine, Taipei Medical University, Taipei; ²Chi-Mei Medical Center, Tainan; ³Department of Pharmacy, National Taiwan University Hospital, Taipei; and ⁴Cardiology Section, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan

Submitted 26 July 2007 ; accepted in final form 13 September 2007

We assessed whether pravastatin attenuates cardiac sympathetic reinnervation after myocardial infarction through the activation of ATP-sensitive K⁺ (K_ATP) channels. Epidemiological studies have shown that men treated with statins appear to have a lower incidence of sudden death than men without statins. However, the specific factor for this has remained disappointingly elusive. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to groups treated with either vehicle, nicorandil (a specific mitochondrial K_ATP channel agonist), pinacidil (a nonspecific K_ATP channel agonist), pravastatin, glibenclamide (a K_ATP channel blocker), or a combination of nicorandil and glibenclamide, pinacidil and glibenclamide, or pravastatin and glibenclamide for 4 wk. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats at the remote zone compared with sham-operated rats (2.54 ± 0.17 vs. 1.26 ± 0.36 µg/g protein, P < 0.0001), consistent with excessive sympathetic reinnervation after infarction. 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 tyrosine hydroxylase protein expression and mRNA in vehicle-treated rats, which was reduced after the administration of either nicorandil, pinacidil, or pravastatin. Arrhythmic scores during programmed stimulation in vehicle-treated rats were significantly higher than those treated with pravastatin. In contrast, the beneficial effects of pravastatin were reversed by the addition of glibenclamide, implicating K_ATP channels as the relevant target. The sympathetic reinnervation after infarction is modulated by the activation of K_ATP channels. Chronic use of pravastatin after infarction, resulting in attenuated sympathetic reinnervation by the activation of K_ATP channels, may modify the arrhythomogenic response to programmed electrical stimulation.

immunohistochemistry; ion channels; myocardial infarction; norepinephrine; polymerase chain reaction