ROLE OF CALCIUM IN STRETCH-INDUCED RELEASE AND MESSENGER-RNA SYNTHESIS OF NATRIURETIC PEPTIDES IN ISOLATED RAT ATRIUM

To investigate the role of Ca2+ in stretch-induced synthesis and relea se of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) isolated superfused rat atria were stretched by raising intra-at rial pressure. The immunoreactive (ir-) ANP and BNP concentrations wer e analysed by radioimmunoassay and the corresponding mRNA levels were quantified by Northern blot and dot blot analyses. Stretch-induced ir- ANP release and a rise in BNP mRNA levels increased at high (3.0 mM) c ompared to low (0.5 mM) extracellular Ca2+ concentration ([Ca2+](o)). Moreover, the adaptation of stretch-induced ir-ANP release was depende nt on [Ca2+](o). Atrial BNP mRNA levels were increased by stretch also in non-paced, electrically silent atria, where voltage-activated Ca2 channels are not activated. The stretch-induced rise in BNP mRNA was blocked by gadolinium (80 mu M), but not by the L-type channel blocker diltiazem (3.0 mu M). This study indicates that both the stretch-secr etion coupling of ir-ANP release and the pressure-stimulated synthesis of BNP mRNA are Ca2+-dependent processes. Gadolinium inhibits the str etch-stimulated rise in BNP mRNA levels in contracting and non-contrac ting atria, which is similar to its ability to block stretch-activated ir-ANP release, suggesting the involvement of Ca2+-permeable stretch- activated channels.