Figure 1.

Regulation of vasodilation by nitric oxide and soluble guanylyl cyclase. Nitric oxide (NO) is generated in the endothelium, diffuses into smooth muscle, binds to soluble guanylyl cyclase (sGC), where it induces a conformational change that catalyzes the generation cyclic guanosine monophosphate (cGMP). cGMP activates subsequent kinases resulting in vasodilation. Phosphodiesterase 5 (PDE–5) metabolizes cGMP. Hypoxia and shear stress stimulate endothelium-mediated vasodilation, whereas hyperoxia, oxidative damage, and trauma impair NO–mediated vasodilation.