Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle

Abstract

A novel vasodilating agent, vinpocetine (14-ethoxycarbonyl-(3 alpha,16 alpha-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 microM, 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.