Involvement of calcium in cyclic nucleotide metabolism in human vascular smooth muscle

When cyclic nucleotide phosphodiesterase was purified from isolated smooth muscle layer of human aorta by DEAE-cellulose column chromatography, separated cyclic GMP phosphodiesterase activity was markedly stimulated in the presence of 10-20 micrometer of Ca2+ by a protein modulator which has similar physicochemical properties to troponin C. Synthetic compound, N-(6-aminohexl)-5-chloro-1-naphthalensulfonamide, which produced relaxations of arteries contracted by prostaglandin F2alpha or KCl was found to inhibit selectively this Ca2+-dependent cyclic GMP phosphodiesterase. This compound produced inhibition of superprecipitation of myosin B system obtained from mouse skeletal muscle and also inhibited adenosine triphosphatase activity of myosin B. Our data suggest that calcium is involved through a protein modulator in cyclic nucleotide metabolism of vascular smooth muscle and that the calcium-dependent protein modulator probably participates in the regulation of contractile response of vascular smooth muscle by affecting actomyosin ATPase activity.