It is increasingly recognized that neuronal production of nitric oxide (NO) can influence cardiovascular homeostasis through its action as a neuromodulator within the autonomic nervous system. Current data suggest that neuronal NO production is impaired in pathological states such as hypertension.

Gene transfer of neuronal nitric oxide synthase (nNOS) with viral vectors that can cause promiscuous transfection have been used to implicate a role for NO in the autonomic control of cardiac excitability. We provide direct evidence that nNOS targeted to only cardiac sympathetic neurons can inhibit noradrenergic neurotransmission. Adenovirus constructed with a noradrenergic specific promoter (PRSx8) coupled to nNOS or enhanced green fluorescence protein (eGFP) caused exclusive expression in cardiac sympathetic neurons. nNOS activity in AdPRS-nNOS group was higher than AdPRS-eGFP group. Functionally, we observed the AdPRS-nNOS mediated nNOS gene transfer significantly reduced evoked noradrenaline release in response to field stimulation of isolated right atria. NOS inhibition reversed this response. These results demonstrate that noradrenergic cell specific gene transfer with nNOS can increase NOS activity resulting in inhibition of cardiac sympathetic transmission, and that this targeted technique may provide a novel method for reducing sympathetic hyperactivity in pathological state.