Role of the nitric oxide (NO)/cGMP signaling in the relaxations of mouse corpus cavernosum (CC) induced by the soluble guanylyl cyclase stimulator (sGC) BAY 41‐2272.

Abstract

OBJECTIVE To characterize the in vitro effects of the NO-independent sGC stimulator BAY 41-2272 on CC from wild-type (WT), nNOS −/− and eNOS −/− mice. METHODS CC strips were mounted in 4-ml myographs and isometric force was recorded. cGMP was measured using EIA kits. RESULTS BAY 41-2272 (0.01–10 μM) relaxed CC with pEC50 values of 6.34±0.04, 6.36±0.06 and 5.70±0.07 in WT, nNOS μ/μ and eNOS μ/μ mice, respectively. L-NAME (100 μM) rightward shifted the curves to BAY 41-2272 by 3-fold in CC from WT and nNOS μ/μ, but not eNOS μ/μ. ODQ (10 μM) reduced BAY 41-2272-evoked relaxations as evidenced by rightward shifts of 4-fold. Sildenafil (0.1 μM) potentiated the relaxations induced by BAY 41-2272 in all groups. BAY 41-2272 (0.1 μM) enhanced SNP-induced relaxations of CC from WT (CTL: 6.58±0.05; BAY: 7.06±0.01), nNOS μ/μ (CTL: 6.47±0.06; BAY: 6.84±0.03) and eNOS μ/μ (CTL: 6.74±0.04; BAY: 7.16±0.03). BAY 41-2272 potentiated acetylcholine (ACh, 0.01–1 μM)- and electrical field stimulation (EFS, 1–16 Hz)-induced relaxations. BAY 41-2272 (1 μM) caused a 30-fold increase in cGMP concentration in WT and nNOS −/− samples versus an 18-fold increase in eNOS −/− CC. Co-incubation with SNP (1 μM) resulted in a synergistic increase in cGMP levels in an ODQ-sensitive manner. CONCLUSION sGC activation in the penis by BAY 41-2272 directly or via enhancement of NO effects may provide a novel treatment for erectile dysfunction. Support: HL74167, AHA.