The Role of Diadenosine Pentaphosphate and Nicotinamide Adenine Dinucleotide (NAD plus ) as Potential Nucleotide Comediators in the Adrenergic Regulation of Cardiac Function

The functioning of the heart is under the tight control of the sympathetic division of the autonomous nervous system. The terminals of the postganglionary fibers release both noradrenaline (NA), which is the major sympathetic neurotransmitter, and comediators that can contribute to the fine "tuning" of the adrenergic control of cardiac function. Purine compounds, such as diadenosine pentaphosphate (Ap5A), as well as nicotinamide adenine dinucleotide (NAD+), can act as comediators. The distinctive features of the effects of these compounds on the heart have been incompletely characterized. It is not clear whether these compounds can act as comediators, i.e., to modulate the sympathetic (adrenergic) activity in the heart. Exogenous extracellular Ap5A was shown to reduce the contractility of the ventricular myocardium and to suppress conduction in the atrioventricular (AV) junction in a Langendorff-perfused isolated rat heart. Extracellular NAD(+) had a weak effect on inotropy but induced a negative dromotropic effect in the AV junction, similarly to Ap5A. We found that Ap5A and NAD+ suppress both the positive inotropic effect of noradrenaline in the ventricular myocardium and the positive dromotropic effect of NA in the AV junction. The "inhibitory" effects of both purine compounds were more pronounced in the case of combined application with NA. In addition, the influence of Ap5A and NAD(+) on the effects of noradrenaline was shown to depend on the timing of the application of these compounds. Our results suggest that the role of the sympathetic comediators NAD(+) and Ap5A may consist of the limitation of noradrenaline effects and/or the effects of sympathetic stimulation in the heart.