Fig. 1.

A NO and sGC activators target two different redox states of sGC: the NO-sensitive reduced native sGC and the NO-insensitive oxidized and finally heme-free apo-sGC, respectively. NO stabilizes the nitrosyl-heme complex of the reduced sGC to increase cGMP. Activators of sGC such as mosliciguat (B) bind to the unoccupied heme-binding complex or displace the prosthetic heme of sGC. The inhaled sGC activator is activating the heme-free apo-sGC to increase cGMP which mediates vasorelaxation and bronchodilation and blocks remodelling, apoptosis, and inflammation. ARDS acute respiratory distress syndrome, cGMP cyclic guanosine monophosphate, NO nitric oxide, PPHN persistent pulmonary hypertension in the neonate, sGC soluble guanylate cyclase