Heterotrimeric G proteins are the molecular switches in the receptor-mediated transmembrane signaling system. Inducible nitric oxide synthase (iNOS) is inducible by a variety of inflammatory stimuli, which leads to vascular hyporeactivity. In this chapter, the system to study the cell signaling pathways downstream of the GPCR coupling to G proteins is described for the study of iNOS gene expression. The cellular signaling pathways by which ligand induces iNOS may serve as the pharmacological targets for preventing or treating vascular hyporeactivity.