Background: Soluble guanylyl cyclase (sGC) is expressed in mammalian cytoplasm and catalyzes the synthesis of the second messenger guanosine 3',5'-monophosphate (cGMP) involved in important physiological functions such as relaxation of vascular smooth muscle, inhibition of platelet aggregation, modulation of inflammation, and control of vascular permeability. sGC is the intracellular receptor for nitric oxide (NO) and the active moiety in traditional organic nitrate therapy, recently as an inhalant in the intensive care unit and experimentally in improving microcirculatory flow in shock. However, dysfunction of the heme moiety on sGC occurs in a number of cardiovascular diseases, which reduces NO effectiveness.
Methods: In this review, we examine animal studies and early clinical trials on agents that can directly stimulate sGC and may have future clinical application in cardiovascular disease and in perioperative care.
Conclusions: Animal and early clinical studies have shown that sGC stimulator agents have great promise for treating cardiopulmonary disorders and may also have a role in modulating the inflammatory response observed in perioperative care.
Keywords: Cardiovascular diseases; drug tolerance; inflammation; nitric oxide; nitric oxide donors; nitroglycerin; pulmonary hypertension; soluble guanylyl cyclase.