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 alpha and a beta subunit. For both subunits two isoforms have been characterized, but only the sGC alpha(1)beta(1) and sGC alpha(2)beta(1) isoforms seem to be functionally active. To elucidate the functional role of the sGC alpha(1)beta(1) heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGC alpha (1) (-/-) mice. For the in vivo study sGC-dependent and -independent vasorelaxing agents were injected intracavernosally in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice and the rise in intracavernosal pressure was recorded. For the in vitro study, isolated CC tissues from sGC alpha (1) (-/-) and sGC alpha (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 sGC alpha (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 sGC alpha (1) (-/-) and sGC alpha (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 sGC alpha(1)beta(1) heterodimer, although remaining vasorelaxing responses in the sGC alpha (1) (-/-) mice suggest a complementary role for the sGC alpha(2)beta(1) isoform or (an) sGC-independent mechanism(s)