Atriopeptin II and 8-bromo-cGMP lower Ca2+ in cultured aortic smooth muscle cells

Atriopeptin II (ANP) or 8-Bromo-cGMP (8-Br-cGMP) decreased the levels of intracellular Ca2+ in Angiotensin II- (Ang) or K+-stimulated cultured rat aortic smooth muscle cells. Cytoplasmic Ca2+, measured by fura-2 fluorescence, was maximal at 30 to 60 sec following the addition of either Ang or KCl. Pretreatment of smooth muscle cells with ANP or 8-Br-cGMP diminished peak levels of Ca2+ in response to Ang or KCl. Because the source of Ca2+ mobilized by KCl was extracellular while that mobilized by Ang was intracellular, these results suggested that ANP and 8-Br-cGMP did not inhibit the mobilization of Ca2+. This was further supported by studies on the effects of ANP and 8-Br-cGMP on inositol polyphosphate production in cells labelled with 3H-inositol. Ang, but not KCl, produced time-dependent increases in inositol polyphosphates. On the other hand, they have observed that cGMP-dependent protein kinase (cGPK), but not cAMP-dependent protein kinase, caused a 4-fold stimulation of Ca2+ ATPase activity in crude microsomal fractions from cultured rat aortic smooth muscle cells. These results suggest that ANP and 8-Br-cGMP may lower Ca2+ mobilized by Ang or KCl by enhancing Ca2+ efflux or resequestration possibly through the stimulation of a Ca2+ ATPase pump