Chronic heart disease increases neuronal and inducible nitric oxide synthase expression within the intrinsic cardiac plexus of the guinea pig

Chronic heart disease induces functional and phenotypic remodeling of neurons contained within the cardiac nervous system, including those contained within the intrinsic cardiac ganglionated plexus, and the cardiac tissues it innervates. Specifically, either surgically‐induced chronic myocardial infarction (MI) or pressure overload (PO) increased the number of intracardiac neurons expressing neuronal nitric oxide synthase (nNOS), as detected by immunohistochemistry, with increased expression of inducible (iNOS) restricted to neurons derived from animals with chronic MI. The present study quantified the changes in mRNA production and protein expression of both nNOS and iNOS in neurons contained within the intrinsic cardiac plexus in normal/sham control animals as compared to guinea pigs with 8 weeks of chronic MI or PO. Quantitative PCR analysis of nNOS mRNA expression showed significant increases after MI (2.3‐fold) and PO (3.2‐fold) when normalized to control genes 18S and GAPDH. In contrast, iNOS mRNA expression significantly increased only after MI (3.5‐fold). These results support the qualitative changes observed with immunohistochemical analysis and suggest that part of the remodeling in cardiac‐related neurons includes significant changes in gene expression of important modulators of neuronal function. Supported by NIH HL98589 to JCH and EMS and HL71830 to JLA.