Abstract
5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1 H-pyrazolo[3,4- b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01–10 μM) relaxed both rabbit (pEC 50=6.82±0.06) and human (pEC 50=6.12±0.10) precontracted cavernosal strips. The guanylyl cyclase inhibitor (ODQ, 10 μM) caused significant rightward shifts in the concentration–response curves for BAY 41-2272 in rabbit (4.7-fold) and human (2.3-fold) tissues. The NO synthesis inhibitor ( N-nitro- l-arginine methyl ester ( l-NAME), 100 μM) also produced similar rightward shifts, revealing that BAY 41-2272 acts synergistically with endogenous NO to elicit its relaxant effect. The results also indicate that ODQ is selective for the NO-stimulated enzyme, since relaxations evoked by BAY 41-2272 were only partly attenuated by ODQ. The present study shows that both BAY 41-2272 and sildenafil evoke relaxations independent of inhibition of haem in soluble guanylate cyclase. Moreover, there is no synergistic effect of the two compounds in corpus cavernosum.
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