Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle

A novel vasodilating agent, vinpocetine (14-ethoxycarbonyl-(3α, 16α-ethyl-14, 15-eburnamenine) inhibits Ca²⁺-dependent phosphodiesterase, selectively, among the three forms of cyclic nucleotide phosphodiesterase identified in the rabbit aorta. The concentration of vinpocetine producing 50% inhibition of Ca²⁺-dependent phosphodiesterase activity was approximately 21 μM, both in the presence and absence of Ca²⁺-calmodulin (CaM). Increasing the concentration of CaM in the presence of Ca²⁺ did not prevent vinpocetine-induced inhibition of Ca²⁺-dependent phosphodiesterase, thereby indicating that vinpocetine inhibited the enzyme by interacting with the enzyme and not with CaM. To determine the influence of vinpocetine-induced inhibition of Ca²⁺-dependent phosphodiesterase on cyclic nucleotide metabolism in vascular smooth muscle, cyclic nucleotide levels in isolated rabbit aortic strips were also investigated. Addition of vinpocetine produced dose-dependent increases in only the cyclic GMP levels and there was no significant effects on the cyclic AMP levels. These results provide pharmacological evidence that Ca²⁺-dependent phosphodiesterase mainly hydrolyzes cyclic GMP in vascular smooth muscle. Vinpocetine may induce vascular relaxation by increasing cyclic GMP contents in vascular smooth muscle through selective inhibition of Ca²⁺-dependent phosphodiesterase.