Mechanisms of release and renal action of atrial natriuretic factor

In addition to the well-documented stretch-induced secretion of atrial natriuretic factor (ANF), we have shown that addition of agonists such as vasopressin or angiotensin, added to incubation medium with freshly excised rat atria, caused marked release of the hormone in vitro. Others have had difficulty in reproducing these results. In experiments designed to address this problem we found that removal of the atrial endothelium was necessary to demonstrate agonist-induced release of ANF. The results suggest that the endothelial lining of atrial tissue may limit access of the agonists to the myocytes, and thereby play a modulating role in receptor-stimulated secretion of the hormone. The renal mechanism of action of ANF includes inhibition of Na transport in the medullary collecting duct (MCD). Recent in vitro studies have suggested that this inhibition occurs via blockade of amiloride-sensitive Na channels. However, ANF-induced reduction of MCD transport in vivo is much greater than that obtainable with amiloride. Although, by luminal administration of ANF in vivo, we were able to confirm an amiloride-like action of the hormone at this site, we could not thereby mimic the effects of systemic ANF on MCD Na reabsorption. The results thus indicate that a peritubular effect is an important determinant of ANF natriuresis.