Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease

Jan R. Kraehling, William C. Sessa

Mechanism of action of nitric oxide–sensitive guanylate cyclase (NOsGC) stimulators and activators. NOsGC stimulators bind to the enzyme and act in an allosteric manner. NO and NOsGC stimulators enhance the NOsGC activity synergistically. NOsGC activators occupy the heme binding site and work therefore only additively with NO. The oxidation of the heme-Fe2+ to heme-Fe3+ results in a weaker binding of heme to NOsGC, hence allowing the NOsGC activators to occupy the heme binding site easier. The schematic is derived from Zorn and Wells.111 [Powerpoint File]

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