MODULATION OF INTRINSIC CARDIAC NEURONAL-ACTIVITY BY NITRIC-OXIDE DONORS INDUCES CARDIODYNAMIC CHANGES

Studies were performed to determine 1) whether a specific marker for nitric oxide production is associated with canine intrinsic cardiac neurons, 2) whether the transmembrane properties of these neurons can be altered by nitric oxide donors, 3) whether in situ intrinsic cardiac neurons are sensitive to nitric oxide donors, and 4) whether these neurons are involved in cardiac regulation. Thirty to forty percent of canine intrinsic cardiac neurons were labeled with a selective anatomic marker for nitric oxide production. Nitric oxide donors modified the transmembrane properties of a subpopulation of intrinsic cardiac neurons studied in vitro. The nitric oxide donors nitroglycerine, sodium nitrite, and nitroprusside induced concentration-dependent increases in neuronal activity frequently associated with cardiac augmentation. Similar neuronal responses were elicited by N-methyl-D-aspartate receptor activation as well as when the precursor of nitric oxide, L-arginine, and the exogenous nitric oxide donor, S-nitroso-N-acetylpenicillamine, were administered, indicating that intrinsic cardiac neurons can be modulated by nitric oxide donors. Such neurons apparently are tonically influenced by locally released nitric oxide as local administration of the competitive inhibitor of nitric oxide synthase, N-G-nitro-L-arginine methyl ester, suppressed their spontaneous activity. These data indicate that a significant population of nitric oxide-sensitive neurons exists in the canine intrinsic cardiac nervous system that are involved in cardiac regulation.