Role of calcium in stretch-induced release and mRNA synthesis of natriuretic peptides in isolated rat atrium

 To investigate the role of Ca²⁺ in stretch-induced synthesis and release of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) isolated superfused rat atria were stretched by raising intra-atrial pressure. The immunoreactive (ir-) ANP and BNP concentrations were 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) compared to low (0.5 mM) extracellular Ca²⁺ concentration (Ca²⁺]_o). Moreover, the adaptation of stretch-induced ir-ANP release was dependent 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 μM), but not by the L-type channel blocker diltiazem (3.0 μM). This study indicates that both the stretch-secretion coupling of ir-ANP release and the pressure-stimulated synthesis of BNP mRNA are Ca²⁺-dependent processes. Gadolinium inhibits the stretch-stimulated rise in BNP mRNA levels in contracting and non-contracting atria, which is similar to its ability to block stretch-activated ir-ANP release, suggesting the involvement of Ca²⁺-permeable stretch-activated channels. Received: 29 April 1996 / Received after revision and accepted: 17 June 1996