Fig. 1. Nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signal transduction pathway. NO, formed by endothelial cells (  left ) or administered by inhalation (  right ), diffuses to vascular smooth muscle cells (  lower ). NO activates soluble guanylate cyclase, which in turn catalyzes the production of cGMP. Through cGMP-dependent protein kinase mediated effects, increased intracellular concentration of cGMP relaxes smooth muscle and inhibits leukocyte adhesion, platelet adhesion, and cellular proliferation. The action of cGMP is limited by phosphodiesterases, which convert cGMP to GMP.