Analysis of the direct and indirect effects of adenosine on atrial and ventricular cardiac muscle.
The effects of adenosine were examined upon the tension developed by isolated paced left atria, left ventricular papillary muscles, and right ventricular strips, and upon the spontaneous rate of contraction of right atria of guinea pigs. Three aspects of the direct and indirect actions were examined: the direct effects upon resting developed tension and rate, the indirect activity when added to tissues prestimulated by isoprenaline, and the indirect activity upon isoprenaline concentration--response curves when added prior to exposure to isoprenaline. The direct effects on the atria were decreases in left atrial tension and right atrial rate. These responses were antagonized by 8-phenyltheophylline (8-PT) and therefore were due to stimulation of cell surface P1 purinoceptors. This antagonism was greater in the left atria than the right. The direct ventricular effects were, in contrast, increases in force of contraction, which were not antagonized by 8-PT. This positive inotropy was also unaffected by reserpine pretreatment of the guinea pigs and therefore not due to release of endogenous catecholamines. A possible intracellular effect of adenosine is discussed. Adenosine reduced the isoprenaline-prestimulated tension or rate in both atrial and ventricular tissues, and this indirect effect was susceptible to antagonism by 8-PT. In the presence of adenosine, concentration-response curves of the left and right atria for isoprenaline were displaced to the right, and the maxima were reduced. In contrast, there was no antagonism of the papillary muscle curves to isoprenaline, but the maximum developed tension was elevated. The minimal inhibitory effects of adenosine in ventricular muscles and the high concentrations required are discussed in the context of a physiological role for endogenous adenosine in attenuating cardiac overstimulation by the sympathetic nervous system or endogenously released catecholamines.