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 mug/
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.