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

Studies were performed to determine 1) whether a specific marker for n itric oxide production is associated with canine intrinsic cardiac neu rons, 2) whether the transmembrane properties of these neurons can be altered by nitric oxide donors, 3) whether in situ intrinsic cardiac n eurons are sensitive to nitric oxide donors, and 4) whether these neur ons are involved in cardiac regulation. Thirty to forty percent of can ine intrinsic cardiac neurons were labeled with a selective anatomic m arker for nitric oxide production. Nitric oxide donors modified the tr ansmembrane properties of a subpopulation of intrinsic cardiac neurons studied in vitro. The nitric oxide donors nitroglycerine, sodium nitr ite, and nitroprusside induced concentration-dependent increases in ne uronal activity frequently associated with cardiac augmentation. Simil ar neuronal responses were elicited by N-methyl-D-aspartate receptor a ctivation as well as when the precursor of nitric oxide, L-arginine, a nd the exogenous nitric oxide donor, S-nitroso-N-acetylpenicillamine, were administered, indicating that intrinsic cardiac neurons can be mo dulated 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-argin ine methyl ester, suppressed their spontaneous activity. These data in dicate that a significant population of nitric oxide-sensitive neurons exists in the canine intrinsic cardiac nervous system that are involv ed in cardiac regulation.