The effects of atriopeptin II on calcium fluxes in rabbit aorta

Effects of atriopeptin II (AP II) at 10(-7) M on the 45Ca flux and contractile responses to vasoconstrictors including norepinephrine (NE), angiotensin II (angio II) and high K were studied in isolated rabbit aortic strips. Augmentation of 45Ca efflux from aorta in normal physiological saline (PSS) due to NE and angio II each at 3 X 10(-7) M was greatly inhibited by AP II, suggesting that stimulated increase in cytosolic Ca2+ was suppressed. In contrast, the 45Ca efflux responses to KCl (20 and 40 mM) were not affected by AP II. Furthermore, the marked inhibition of contractile responses to NE (-58%) and angio II (-57%) by AP II was accompanied by significant decreases in 45Ca influx, whereas AP II exhibited only a modest inhibition on KCl (40 mM)-induced contraction (-28%) without affecting the accompanying increase in 45Ca influx. The 45Ca efflux from aortae in Ca2+-free PSS due to NE was markedly diminished by AP II, suggesting impairment of intracellular Ca2+ release. With tissues in either a basal or post-stimulation state (tissue Ca2+ previously increased with KCl stimulation), AP II did not stimulate 45Ca efflux in Ca2+-free PSS, suggesting its lack of effect on Ca extrusion. It is concluded that AP II is preferentially antagonistic against vascular responses to NE and angio II vs. high K and that inhibition of Ca entry and release forms the primary basis of its potent vasorelaxant action against vasoconstrictors.