Molecular Mechanisms of Cardiostimulatory Effects of Sildenafil
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To better understand the molecular mechanisms of the previously described cardiostimulatory action of the phosphodiesterase type-5 (PDE5) inhibitor sildenafil, we first evaluated its effects on cyclic AMP level in the canine ventricular membrane preparation. Sildenafil (10 μmol/L) significantly increased the net cyclic AMP production rate, the potency of which was similar to that of 3-isobutyl-1-methylxanthine (IBMX). Next, we assessed the inhibitory effect of sildenafil on PDE of bovine heart. Sildenafil (≥1 μmol/L) as well as IBMX significantly decreased the cyclic AMP hydrolyzing speed of PDE. These results suggest that a supra-therapeutic concentration of sildenafil may directly inhibit cyclic AMP hydrolyzing PDEs in the heart, although indirect inhibition of PDE3 via the “cross-talk” pathway cannot be totally excluded.
- The Japanese Journal of Pharmacology
The Japanese Journal of Pharmacology 88(3), 362-364, 2002-03-01
The Japanese Pharmacological Society