The cardiocytes of mammalian cardiac atria contain granules very similar to those in endocrine cells. The number of these atrial granules is related directly to salt loading and blood volume. Furthermore, crude extracts of rat atria and granule preparations have powerful natriuretic and diuretic effects. These effects are mediated by peptides identified previously as atrial natriuretic factor (ANF). The peptides are derived from a common precursor, whose structure has been elucidated recently. Although there is indirect evidence from morphological studies that at least some of these peptides may be released into the blood and function as hormones, their presence in the blood has not yet been demonstrated. Here we describe a sensitive and specific radioimmunoassay for ANF and its stimulation on volume loading.

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.

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