The enzyme soluble guanylate cyclase (sGC) is the only known nitric oxide (NO) receptor in the human body. Nitric oxide is formed in the endothelium – a thin layer of cells on the inside of blood vessels – and plays an important role in the human cardiovascular system.
Nitric oxide activates soluble guanylate cyclase, which in turn initiates the production of the messenger cGMP (cyclic guanosine monophosphate). cGMP causes the smooth muscle cells in the vessel walls to relax (vasodilation), so that the blood pressure falls. In addition the messenger counteracts cramp, thickening of the vessel walls, and the depositing of platelets and connective-tissue cells, which can clog the blood vessels and reduce their elasticity. cGMP also inhibits excessive cell proliferation and inflammation.
If little or no nitric oxide is present, because the endothelium is not functioning properly (endothelial dysfunction), the signal pathway cannot be activated. The result is a cGMP deficiency, which leads to a narrowing of the blood vessels and to pathological changes in the vessel walls – as a result, for example, of blood clots, scarring or inflammation. These changes in the vessel walls cause further damage to the endothelium.
Disruption of this so-called NO-sGC-cGMP signaling pathway is behind several forms of pulmonary hypertension, and also plays a role in the pathogenesis of coronary heart disease and other vascular diseases.
Because of its key function in the course of such diseases, soluble guanylate cyclase is a promising molecule for pharmaceutical research. Drugs that sensitize the enzyme for existing nitric oxide, or activate it independently of nitric oxide, can restore the signaling pathway and counteract the pathological processes in the vessels.
Bayer is engaged in research in the field of soluble guanylate cyclase.