The Effect of Atrial Natriuretic Peptide on Cytosolic Free Calcium in Cultured Vascular Smooth Muscle Cells

Effect of atrial natriuretic peptide (ANP) on cytosolic free calcium ([Ca²⁺]i) was studied in monolayers of cultured vascular smooth muscle (VSM) cells loaded with a fluorescent calcium indicator, fura-2. Vasoconstrictive hormones, angiotensin II (AII) and Arg⁸-vasopressin (AVP) induced initial rapid rises in [Ca²⁺]i, followed by sustained elevation of [Ca²⁺]i. ANP (Atriopeptin III 10^-8M) decreased both the resting level and the sustained elevation of [Ca²⁺]i induced by AII and AVP. ANP also decreased the rise in [Ca²⁺]i induced by high potassium (K⁺) depolarization. AVP-induced initial rapid rise in [Ca²⁺]i was not inhibited by ANP in the presence or absence of the phosphodiesterase inhibitor, isobutylmethylxanthine 0.1 mM, which has been shown to fully enhance ANP-induced cyclic GMP accumulation. On the other hand, a calcium antagonist, nicardipine, inhibited the high K⁺-induced rise in [Ca²⁺]i, whereas it had no effect on not only initial but also sustained rises in [Ca²⁺]i induced by AVP or AII. These results suggest that ANP has an ability to decrease [Ca²⁺]i not through inhibition of voltage-sensitive calcium channels, and that neither ANP nor ANP-induced cyclic GMP may affect initial hormone-induced rise in [Ca²⁺]i. In conclusion, an ability to decrease [Ca²⁺]i is implicated in ANP-induced relaxation of VSM.