Novel non-NO-dependent sGC stimulators can increase the activity of sGC

Organic nitrate therapy and inhaled NO can stimulate soluble guanylyl cyclase (sGC) when the heme moiety on sGC is in a reduced (ferrous) state.

Agonists such as acetylcholine, bradykinin, and serotonin encourage the production of nitric oxide (NO) though activation of nitric oxide synthase (NOS).

NO-sGC-cGMP pathway.

Система NO-растворимая ГЦ-цГМФ

Activated sGC stimulates production of cyclic guanosine 3′,5′-monophosphate (cGMP) that through downstream mechanisms elicit relaxation of vascular smooth muscle, inhibition of platelet aggregation, modulation of inflammation, and control of vascular permeability. Phosphodiesterases (PDEs) break down cGMP. Oxidation of the heme moiety in sGC from stress, aging, injury, and the development of tolerance from organic nitrates reduce sGC activation. PDEs break down cGMP, whereas PDE5 inhibitors prevent the breakdown of cGMP.

Дата добавления: 2014-01-14