In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection

Abstract

Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an α and a β subunit. For both subunits two isoforms have been characterized, but only the sGCα(1)β(1) and sGCα(2)β(1) isoforms seem to be functionally active. To elucidate the functional role of the sGCα(1)β(1) heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGCα(1)(-/-) mice. For the in vivo study sGC-dependent and -independent vasorelaxing agents were injected intracavernosally in sGCα(1)(-/-) and sGCα(1)(+/+) mice and the rise in intracavernosal pressure was recorded. For the in vitro study, isolated CC tissues from sGCα(1)(-/-) and sGCα(1)(+/+) mice were mounted in organ baths for isometric tension recording and concentration-dependent curves were obtained for sGC-dependent and -independent vasorelaxing agents. These experiments were performed on 2 different mice strains (129SvEvS7 and C57BL6/J) to determine potential strain differences. The responses in sGCα(1)(-/-) after administration of the NO-donors, sodium nitroprusside (SNP) and spermine-NO, and to electrical stimulation are significantly reduced although not completely abolished. Responses to sGC-independent vasorelaxing agents are similar in sGCα(1)(-/-) and sGCα(1)(+/+) mice from both strains suggesting that the decreased potential of smooth muscle relaxation is not related to structural changes or changes in the pathway downstream sGC. This study illustrates the strain-independent importance of the sGCα(1)β(1) heterodimer, although remaining vasorelaxing responses in the sGCα(1)(-/-) mice suggest a complementary role for the sGCα(2)β(1) isoform or (an) sGC-independent mechanism(s).