Figure 2.

Crosstalk among NO/CO/H₂S/sGC pathways in vascular tissues including the penis. Bold fonts indicate the evidence obtainded in the penis. 1: CO inhibits eNOS in the presence of higher amounts of NO. However, CO activates eNOS when there is a low amount of NO (renal arteries; Botros and Navar, 2006). 2: High levels of CO inhibit NOS activity and NO generation, lower concentrations of CO induce release of NO (Thorup et al., 1999). 3: NO donors activate HO-1 (Foresti and Motterlini, 1999). 4: NO donors up-regulate the expression and activity of CSE in vascular tissues and cultured aortic smooth muscle cells (Leffler et al., 2005 and Zhao et al., 2001). 5: H₂S cause eNOS activation in aorta through Akt. Coletta et al., 2012, and directly increase the expression of eNOS in CC (Meng et al., 2013). 6: CO inhibits CBS sensor (Taoka and Banerjee, 2001). 7: CO modulates NO-stimulated sGC activation dependent on NO concentration. In that, in the presence of low concentrations of NO, CO stimulates, otherwise CO inhibit sGC activation (Kajimura et al., 2003). 8: cGMP causes an increase in H₂S production in vasculature (Bucci et al., 2012). 9: H₂S acts as an endogenous inhibitor of PDE activity (Bucci et al., 2010).