Time-dependent decreases of atrial natriuretic peptide release from the isolated rat atrium: evidence for a readily releasable pool

In vitro, atrial distension causes a rapid increase in atrial natriuretic peptide (ANP) release. This stretch-induced release, however, declines to baseline levels within minutes without significant depletion of the total hormone stores. It has been observed that the basal rate of ANP release from isolated atria also declines over time despite evidence that the tissue retains its viability. We examined this time-dependency of ANP release from isolated rat atria and some parameters that may explain the diminishing release. Mean ANP secretion was 60 pg/min for both spontaneously beating and electrically paced preparations. Although ANP secretion steadily declined over time, there was no time-dependent effect on the amplitude of intracellularly recorded action potentials. The total ANP content in atria obtained after dissection was 133 ± 28.9 μg/g (n = 3) which was not significantly different from atria that were perfused for 3 h (137 ± 21.2 μg/g; n = 3). Only the 28-amino acid circulating form of ANP was released. The ANP mRNA appeared to be partially degraded in atria after 30 min equilibration or after perfusion for 3 h. These results demonstrated that ANP release from isolated atrial preparations declines steadily despite the maintenance of normal electrophysiological activity. This decline was not due to significant depletion of the ANP stores suggesting that a readily releasable pool of ANP exists and represents only a small fraction of the total hormone stores. Finally, degradation of ANP mRNA implies a reduction of de novo synthesis in our preparation which suggests that the observed depletion of the releasable pool was related to a decline in newly synthesized ANP.