Increase in atrial pressure releases atrial natriuretic peptide from isolated perfused rat hearts

To elucidate the mechanism involved in the release of atrial natriuretic peptide, we modified the isolated perfused rat heart preparation to permit a step-wise increase in right atrial tension. Perfusate was introduced into the right atrium through the superior vena cava and was collected via the pulmonary artery. Right atrial pressure was manipulated by changing the perfusion rate. Perfusate from the pulmonary artery was collected in 1-min-fractions, extracted, and assayed for atrial natriuretic peptide like immunoreactivity (ANP-li). The basal rate of ANP-li release at an atrial pressure of 1.41 +/- 0.31 mm Hg was 964 +/- 144 pg/min (n = 11). As right atrial pressure was increased (range 0.4-4.5 mm Hg), a linear correlation (r = 0.85, P less than 0.001) was observed between the change in ANP-li release and the change in atrial pressure. High pressure liquid chromatography revealed that the major fraction in the perfusate had the same elution time than alpha-rANP. This peak fraction, as well as synthetic atriopeptin III, caused a dose-dependent relaxation in rat aortic strips that had been subjected to contraction with norepinephrine. Further, it corresponded exactly to the material we previously identified in rat plasma. These results suggest that atrial distension is involved in the release of ANP. In addition, ANP is released per se, as the active peptide.