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Chronic myocardial infarction induces upregulation of nNOS and alters neuronal excitability in the guinea pig cardiac plexus
Author(s) -
Hardwick Jean C,
Southerland E. Marie,
Ardell Jeffrey L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a523-a
Subject(s) - medicine , myocardial infarction , cardiology , electrophysiology , infarction , autonomic nervous system , depolarization , endocrinology , nitric oxide , neuroscience , biology , heart rate , blood pressure
Chronic myocardial infarction (CMI) is associated with remodeling of the heart and associated autonomic neural control systems. To evaluate the remodeling of the intrinsic cardiac nervous system following myocardial infarction, the dorsal descending coronary artery was ligated in the guinea pig heart and the animals allowed to recover for 6–9 weeks. Thereafter, the cardiac plexus was isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no change in resting membrane properties compared to age‐matched controls. However, the intrinsic cardiac neurons derived from chronic infarcted hearts demonstrated an increase in evoked excitability (as determined by the number of action potentials produced with depolarizing stimuli) and an increase in responses to exogenously applied histamine or pituitary adenylate cyclase‐activating polypeptide (PACAP) as compared to age‐matched controls. The percentage of neurons that demonstrated neuronal nitric oxide (nNOS) immunoreactivity was significantly increased in CMI tissue (17.5 + 5.0% in CMI vs 5.4 + 2.9% in controls; p < 0.02). These results indicate that chronic myocardial infarction induces a differential remodeling of intrinsic cardiac cellular phenotypes and functional up‐regulation of local network excitability. Supported by HL71830 (JLA) and R15 HL060619 ‐02 (JCH).