Mechanism of atriopeptin-induced decrease of cytosolic free Ca in rat vascular smooth muscle cells: evidence for an intracellular locus of action.

The purpose of this study was to investigate the subcellular mechanism of action of atriopeptins in relation to intracellular Ca dynamics. Atriopeptin 23, an analogue of the circulating hormone, decreased cytosolic free Ca in cultured adherent aortic smooth muscle cells, both in the presence and absence of extracellular Ca. Moreover, the atrial peptide did not alter Ca efflux. Atriopeptin 23 decreased the Ca transient induced by angiotensin II (Ang II), but only at low concentrations of the vasoconstrictor peptide. Similar to atriopeptin 23, S-nitroso-N-acetylpenicillamine, an organic nitrovasodilator that increases cGMP levels in vascular tissues, decreased resting Ca in adherent cells, supporting the notion that cGMP is a mediator of atriopeptin action. The results support the concept that atriopeptin decreases intracellular Ca by enhancing intracellular Ca sequestration and/or inhibiting intracellular Ca release.