Abstract 19432: Neuronal Isoform of Nitric Oxide Synthase is Upregulated in Cardiac Intrinsic, and Extrinsic Sympathetic Afferent and Efferent Ganglia Following Myocardial Infarction
Objective: The impact of myocardial infarction (MI) on neuronal nitric oxide synthase (nNOS), an important mediator of cardiac neurotransmission is not well understood.
Methods: Yorkshire pigs (n=10) underwent anterior MI by LAD occlusion. After 6-8 weeks, bilateral stellate ganglia (SG), T1 dorsal root ganglia (DRG), right atrial (RAGP) and ventral inter-ventricular ganglionated plexi (VIVGP)were extracted, formalin-fixed, paraffin-embedded, and sectioned. Immno-staining for nNOS was performed on representative slides through the middle of the ganglia, and for calcitonin-gene related peptide (CGRP), a marker of sensory afferent neurons. The percentage of immunoreactive (IR) neurons was quantified.
Results: An average of 63.1±40.7, 169.7±55.5, and 448.1±204.5 neurons were counted in the GPs, DRG, and SG respectively. There was no significant difference in the number of neurons counted in controls vs MIs. In the GPs, nNOS was differentially altered by MI, with significant upregulation in VIVGP but not RAGP of MI (13.8±2.8% vs 46.6±5.3%, p<0.001; and 12.1±3.6% vs 12.5±2.9%, p=NS, respectively) compared to control animals. In the DRG, IR of both CGRP and nNOS was increased (36.3±6.2% vs 65.3±4.8%, p<0,001 for nNOS; and 64.1±6.2% vs 85.2±5.6%, p<0.001 for CGRP), with increased co-expression of both CGRP and nNOS in approximately 20% of DRG neurons. In the SG, the number of neurons demonstrating strong IR for nNOS was approximately 0.4% in control animals. After MI, this increased 8-fold to 3.12% (P<0.01).
Conclusions: nNOS expression is upregulated differentially following MI in the GPs, with increased expression in the ventricular GP innervating the region of MI, but not in the RAGP. Both cardiac sympathetic afferent (DRG) neurons, and efferent (SG) neurons increase expression of nNOS following MI. The impact of nNOS in these different sites warrants further investigation.
Author Disclosures: K. Nakamura: None. O.A. Ajijola: None. T. Irie: None. K. Yamakawa: None. J. Ardell: None. K. Shivkumar: None.
- © 2015 by American Heart Association, Inc.