Nitric oxide and carbon monoxide synthesizing enzymes and soluble guanylyl cyclase within neurons of adult human cardiac ganglia

Nitric oxide and carbon monoxide are diffusible gas messengers, synthesized by nitric oxide synthase or heme oxygenase 2, respectively, that can activate soluble guanylyl cyclase in adjacent cells. Nitric oxide and carbon monoxide neuromodulation in cardiac ganglia has been demonstrated. However, identification of nitric oxide or carbon monoxide in human cardiac ganglia needs to be confirmed as suggested from animal model studies. Immunohistochemistry was used to demonstrate neuronal nitric oxide synthase, heme oxygenase 2, and soluble guanylyl cyclase immunoreactivity within neurons of adult human cardiac ganglia. Nitric oxide synthase immunoreactivity was present in 37% of neurons within cardiac ganglia, heme oxygenase 2 immunoreactivity in 79%, and soluble guanylyl cyclase in 53%. Our findings support the hypothesis that nitric oxide and carbon monoxide are modulators of neurotransmission in cardiac ganglia and in neural control of the adult human heart.