Fig. 1.

Diagram showing the activation of normally reduced soluble guanylate cyclase (sGC) by nitric oxide (NO), CO, the sGC stimulators YC-1, BAY 41–2272, BAY 41-8543, BAY 60–4552, A-350619, and CFM 1571, and the sGC activators BAY 60-2770, BAY 58–2667. The activation of sGC results in increased conversion of GTP to cGMP and erection. The catalytic activity of the normally reduced enzyme is increased by NO, CO, sGC stimulators, and sGC activators, whereas only sGC activators can increase the catalytic activity of oxidized sGC which is not responsive to NO, CO or sGC stimulators as shown in Figs. 4, 5, 6, and 8. sGC is inactivated by ODQ, which oxidizes the heme iron on the beta subunit of the enzyme and renders it insensitive to NO. The heme oxygenase pathway, which induces erection by generating CO, is also shown.