Actions of the phosphodiesterase inhibitor zardaverine on guinea-pig ventricular muscle

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Abstract
The positive inotropic action of the phosphodiesterase inhibitor zardaverine was investigated in guinea-pig heart muscle. In right papillary muscles, 1–30 μM zardaverine reversibly increased the force of contraction in a concentration-dependent manner. This effect was accompanied by a shortening of contraction and relaxation times. Resting membrane potential was unchanged, whereas action potential amplitude was significantly increased and duration was reduced. In papillary muscles partially depolarised with 22 mM K+, zardaverine (10 and 30 μLM) restored slow action potentials, which were not influenced by cimetidine, propranolol or prazosin but were blocked by the calcium channel blocker (+)-nitrendipine or the muscarinic agonist carbachol. cAMP-specific phosphodiesterase III, isolated from guinea-pig ventricular muscle was inhibited by zardaverine as was cAMP-specific phosphodiesterase IV, isolated from dog trachea (IC50s: 0.5 and 0.8 μM, respectively). The results suggest that the observed positive inotropic and electrophysiological effects result from an inhibition of cellular phosphodiesterase.

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