Dihydropyridine Ca2+ entry blockers selectively inhibit peak I cAMP phosphodiesterase.

The vasodilatory action of Ca2+ entry blockers is due primarily to slow Ca2+ channel inhibition; however, these drugs may have additional sites of action that contribute to vasodilation. Eleven Ca2+ entry blockers were evaluated for their inhibition of the two major forms of bovine heart cAMP phosphodiesterase which were separated by DEAE cellulose chromatography. Nifedipine and four other dihydropyridine Ca2+ entry blockers selectively inhibited peak I phosphodiesterase activity with IC50 values between 2 and 3 microM but were weak inhibitors of peak II phosphodiesterase with IC50 values of 100 microM or greater. The selective inhibition of peak I phosphodiesterase activity by these dihydropyridine Ca2+ entry blockers may be an intracellular mechanism for producing vasodilation in addition to slow Ca2+ channel inhibition.