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Nitric oxide (NO) derived from neuronal nitric oxide synthase (nNOS) facilitates cardiac vagal neurotransmission and bradycardia in vitro. Here we provide evidence of rapid (within 9 h) protein expression and increased vagal responsiveness in vivo following targeted gene transfer of nNOS into the cardiac vagus of the pig. Right vagi were injected with vector encoding nNOS (Ad.nNOS) or saline, while left vagi received an injection of vector encoding enhanced green fluorescent protein (Ad.eGFP). Enhanced nNOS protein expression was detected exclusively in the right vagus nerve, with no evidence of iNOS expression. This was associated with increased baroreflex sensitivity and greater heart rate responsiveness to right vagal stimulation. In contrast, responsiveness of left vagi, or sham-injected right vagi remained constant over the same time period. Basal heart rate was unchanged following gene transfer, suggesting no change in vagal tone. These results support the pre-/post-ganglionic synapse as a site for NO-mediated facilitation of vagal bradycardia in the pig. In addition they demonstrate in vivo that functional gene expression induced with adenoviral vectors occurs earlier than first thought, and may therefore, provide a novel intervention to acutely modulate the neural control of cardiac excitability.

Original publication

DOI

10.1016/j.yjmcc.2005.03.018

Type

Journal article

Journal

J Mol Cell Cardiol

Publication Date

07/2005

Volume

39

Pages

159 - 164

Keywords

Animals, Baroreflex, Bradycardia, Electric Stimulation, Female, Gene Transfer Techniques, Green Fluorescent Proteins, Heart Rate, Male, Nerve Tissue Proteins, Nitric Oxide Synthase, Nitric Oxide Synthase Type I, Parasympathetic Nervous System, Swine, Vagus Nerve