Effects of selective phosphodiesterase inhibitors on isolated coronary, lung and renal arteries from man and rat

The relaxant effects of some isozyme-selective phosphodiesterase inhibitors were evaluated in isolated human and rat coronary, lung and renal arteries. Milrinone and OPC 3911, inhibitors of a cGMP-inhibited cAMP phosphodiesterase (cGI-PDE), were shown to have distinct vasodilator actions. These agents were less potent as relaxants in rat lung and renal arteries than in the corresponding human tissues. OPC 3911, the more potent cGMP-inhibited cAMP phosphodiesterase inhibitor, was found to be the more potent vasorelaxant. Rolipram, a selective inhibitor of a cGMP-noninhibited cAMP phosphodiesterase, had small effects on coronary and lung arteries, but produced a slightly more pronounced relaxation of renal arteries from both man and rat. In human preparations contracted by 30 mM K+, milrinone and OPC 3911 had similar relaxant profiles, and were as potent in coronary as in renal arteries. These results do not support the notion that milrinone has reduced effects on renal vessels in man and show that there may be species differences in vascular responsiveness to cGMP-inhibited cAMP phosphodiesterase inhibitors.