Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

Wohaib Hasan, Peter G. Smith

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1. h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24. h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.

    Original languageEnglish (US)
    Pages (from-to)13-20
    Number of pages8
    JournalAutonomic Neuroscience: Basic and Clinical
    Volume181
    Issue number1
    DOIs
    StatePublished - 2014

    Keywords

    • Adrenergic receptor
    • Autonomic
    • Cardiac ganglion
    • Heart failure
    • Nerve growth factor
    • Parasympathetic

    ASJC Scopus subject areas

    • Endocrine and Autonomic Systems
    • Clinical Neurology
    • Cellular and Molecular Neuroscience

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