BAY 41-2272 was recently identified as a potent soluble guanylate cyclase (sGC) stimulator in a nitric oxide (NO)-independent manner. This study aimed to investigate the effects of BAY 41-2272 in the rabbit (RbCC) and human (HCC) corpus cavernosum. Strips of RbCC and HCC were mounted in organ baths and connected to isometric transducers. Data were recorded in a PowerLab system.

BAY 41-2272 (0.01-10 µM) relaxed both rabbit (pEC₅₀ = 6.82 ± 0.06) and human (pEC₅₀ = 6.12 ± 0.10) in a concentration-dependent manner. The sGC 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 (Figure-1). L-NAME (100 µM) caused a rightward shift in the concentration-response curves to BAY 41-2272 in rabbit (5.9-fold) and human (2.5-fold) tissues. Sildenafil had no significant effect on concentration-response curves for BAY 41-2272. Moreover, incubation of RbCC or HCC with BAY 41-2272 (0.1 µM) did not significantly alter the relaxations elicited by sildenafil. When added simultaneously in rabbit corpus cavernosum the effects of sildenafil and BAY 41-2272 were only additive. The finding that L-NAME reduces BAY 41-2272-evoked relaxations suggests that this compound synergizes with endogenous NO to elicit its erectile response. ODQ solely inhibits the NO-stimulated enzyme. The observation that the effects of BAY 41-2272 and sildenafil are merely additive, suggests the existence of distinct pools of sGC in cavernosal smooth muscle.

Figure 1 - Effects of the soluble guanylyl cyclase (sGC) inhibitor (ODQ, 10 µM) on the relaxations induced by the sGC stimulator BAY 41-2272 (10 nM-10 mM) and the NO donor glyceryl trinitrate (GTN, 10 nM-10 µM) in both rabbit (top panel; n=6) and human (bottom panel; n=6-8) corporeal smooth muscle strips contracted by phenylephrine (PE, 10 µM). Experimental values were obtained in absence (filled symbols) and presence (open symbols) of ODQ, and calculated relative to the maximal changes from the contraction produced by PE in each tissue, which was taken as 100%.