Objective: 

CO as well as the CO-donor CORM-2 possess vasodilatory properties. The objective was to examine the involvement of sGC and its different subunits in CO and CORM-2 induced vasodilatation within different vascular tissues.

Methods: 

Isometric tension recordings were performed on isolated mice aorta, femoral artery as well as corpora cavernosa (CC). To distinguish between the different sGC subunits we evaluated responses to CO and CORM-2 in both sGCa1-/- and sGCb1KI/KI mice and their wild-type controls.

Results: 

CO was unable to relax isolated blood vessels, whereas it induced concentration-dependent relaxations in CC. In CC of wild-type mice, the response to CO was completely inhibited by the sGC inhibitor ODQ. The involvement of sGC was further confirmed by the loss of response to CO in CC isolated from sGCb1KI/KI mice. Moreover, the vasodilatory responses of CO in the corporal tissue of sGCa1-/- mice were strongly inhibited although not completely abolished. In contrast to CO, CORM-2 relaxed all vascular tissues examined. ODQ only partially blocked the response to CORM-2 in the aorta. Interestingly ODQ did not affect the CORM-2 induced relaxation in the femoral arteries and the CC, indicating that sGC is not involved, which was confirmed using the transgenic mice.

Conclusions: 

Vasorelaxation induced by CORM-2 differs from that of CO. While CO-induced vasorelaxation depends on activation of sGC, primarily the sGCa1b1 heterodimer, the vasorelation of CORM-2 is partially or even completely sGC-independent. The observation that CO is more effective in relaxing CC tissues than other cardiovascular tissues suggests that the heme-oxygenase/CO pathway may present a potential new target for treating erectile dysfunction.