EFFECT OF RYANODINE ON ATRIAL-NATRIURETIC-PEPTIDE SECRETION BY CONTRACTING AND QUIESCENT RAT ATRIUM

To elucidate the mechanism involved in the release of atrial natriuret ic peptide (ANP), we studied the importance of ryanodine-sensitive Ca2 + release in stretch-secretion coupling. The experiments were made wit h a left atrial preparation, where the stretch of myocytes was induced by changing the intra-atrial pressure. When external pacing was not a pplied, the atrial preparation was not spontaneously contracting, and it was therefore possible to investigate the secretory mechanism in th e quiescent atrium. The superfusate was collected in 2-min fractions a nd assayed for ANP immunoreactivity. Filtration analysis revealed that the major fraction in the superfusate in all experimental situations had a similar molecular weight as the ANP 1-28. Ryanodine (1.0 mu M an d 0.1 mu M) inhibited stretch-stimulated ANP secretion dose dependentl y both in paced and nonpaced atrium, but did not have any effect on ba sal secretion. The present results support the notion that intracellul ar Ca2+ transients from the intracellular stores are essential for str etch-stimulated ANP secretion, independently from excitation and contr action. Basal ANP secretion is not inhibited by blocking ryanodine-sen sitive Ca2+ channels, either in contracting or in non-contracting atri a. In addition our results confirm that the principal stimulus for ANP secretion in response to atrial distension is the stretch of myocytes . Length shortening of myocytes is not essential for ANP release.