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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus

¹Department of Biology, Ithaca College, Ithaca, New York; and ²Department of Pharmacology, College of Medicine, East Tennessee State University, Johnson City, Tennessee

Submitted 24 March 2008 ; accepted in final form 1 October 2008

Chronic myocardial infarction (CMI) is associated with remodeling of the ventricle and evokes adaption in the cardiac neurohumoral 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 were allowed to recover for 7–9 wk. Thereafter, atrial neurons of the intrinsic cardiac plexus were isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no significant changes in passive membrane properties or action potential configuration compared with age-matched controls and sham-operated animals. The intrinsic cardiac neurons from chronic infarcted hearts did demonstrate an increase in evoked action potential (AP) frequency (as determined by the number of APs produced with depolarizing stimuli) and an increase in responses to exogenously applied histamine compared with sham and age-matched controls. Conversely, pituitary adenylate cyclase-activating polypeptide (PACAP)-induced increases in intrinsic cardiac neuron-evoked AP frequency were similar between control and CMI animals. Immunohistochemical analysis demonstrated a threefold increase in percentage of neurons immunoreactive for neuronal nitric oxide synthase (NOS) in CMI animals compared with control and the additional expression of inducible NOS by some neurons, which was not evident in control animals. Finally, the density of mast cells within the intrinsic cardiac plexus was increased threefold in preparations from CMI animals. These results indicate that CMI induces a differential remodeling of intrinsic cardiac neurons and functional upregulation of neuronal responsiveness to specific neuromodulators.

intrinsic cardiac nervous system; histamine; pituitary adenylate cyclase- activating polypeptide; mast cells; intracellular recording

This article has been cited by other articles:

				J. C. Hardwick, C. N. Baran, E. M. Southerland, and J. L. Ardell Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R859 - R866. [Abstract] [Full Text] [PDF]