BLOCK OF STRETCH-ACTIVATED ATRIAL-NATRIURETIC-PEPTIDE SECRETION BY GADOLINIUM IN ISOLATED RAT ATRIUM

1. Isolated superfused rat atrial preparations were used to study the mechanism of stretch-induced atrial natriuretic peptide (ANP) secretio n. The stretch of the atrial myocytes was induced by raising the intra -atrial pressure. The secretion rates were analysed by measuring ANP c oncentrations from the superfusate fractions by radioimmunoassay. 2. T he effect of gadolinium, a blocker of stretch-activated ion channels, on stretch-induced and basal ANP secretion was investigated by superfu sing the atrial preparation with 5, 20 or 80 mu M GdCl3. Gadolinium de creased stretch-induced ANP secretion in a dose-dependent manner, but did not affect basal secretion. 3. Because high concentrations of gado linium may block voltage-gated calcium channels, we tested whether the selective blockers of L-type (diltiazem) and T-type (NiCl2) calcium c hannels affect the stretch-stimulated ANP release. Neither diltiazem a t 3 mu M nor NiCl2 at 50 mu M affected stretch-induced ANP release in paced atrial preparation. 4. Gadolinium, but not diltiazem, also inhib ited stretch-stimulated ANP secretion in non-paced, quiescent atria. 5 . The findings that ANP release is inhibited by Gd3+, but not by dilti azem or NiCl2, and that the stretch-induced secretion in quiescent atr ia is also inhibited by Gd3+, suggest that stretch-activated ion chann els are involved in the regulation of stretch-induced ANP release.