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Cardiovascular Division, Charles A. Dana Research Institute, Boston, MA.

1. The effects of the vasodilators atrial natriuretic peptide (ANP) and forskolin were determined on isometric force, intracellular ionized Ca2+ concentration ([Ca2+]i) as indicated by aequorin, and myosin light chain (MLC) phosphorylation in ferret aorta. 2. Atrial natriuretic peptide (10(-7) M) inhibited intrinsic tone with an associated significant decrease in [Ca2+]i. ANP also inhibited the contraction induced by KCl with a significant decrease in [Ca2+]i. MLC phosphorylation induced by KCl was inhibited by ANP. 3. Forskolin (10(-6) M) decreased the intrinsic tone without significantly decreasing [Ca2+]i, although MLC phosphorylation was significantly decreased. 4. A calcium-force curve was constructed by plotting the calibrated aequorin light signal against the resulting force. The control (potassium-generated) calcium-force curve was not shifted by ANP, but was significantly shifted to the right by forskolin. Forskolin also shifted the phosphorylation-calcium curve to the right without changing the phosphorylation-force curve. 5. We conclude that the vasodilatory effect of ANP on vascular smooth muscle is mainly due to a decrease in [Ca2+]i. On the other hand, the effect of forskolin is via both a decrease in [Ca2+]i and a change in the Ca2+ requirement for MLC phosphorylation.

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