d be effective in the prevention and possibly treatment of CVDs.

2. Molecular Pathways of NO {#sec2}
===========================

Among the isoforms of NOS, eNOS represents the main source for the NO production in the vasculature. It is predominantly expressed in the endothelium but it has been also detected in kidney, human placenta, cardiomyocytes, platelets, and some neurons \[[@B22]\]. Several endogenous agonists, such as acetylcholine, bradykinin, and vascular endothelial growth factor (VEGF), as well as the shear stress induced by the blood flow, have been reported to activate eNOS \[[@B23]\]. Several studies have demonstrated that the phosphoinositide 3-kinase- (PI3K-) AKT pathway is mainly responsible for eNOS phosphorylation at Ser1177 especially in response to shear stress and VEGF \[[@B24]--[@B26]\]. Moreover, caveolin-1, the main component of the caveolae plasma membranes, has been reported as a negative regulator of eNOS \[[@B27], [@B28]\]. Another mechanism involved in the production of eNOS-derived NO is the activation of the *β*-adrenoreceptors \[[@B29]\] in response to the increase of catecholamines that are expressed at high levels in condition of oxidative stress associated with endothelial dysfunction \[[@B30], [@B31]\].

Neuronal NOS (nNOS) is expressed in specific neurons of the central nervous systems (CNS), as well as in the peripheral nervous systems (PNS) and in perivascular nerve fibers \[[@B32]\]. As in the case of eNOS, nNOS is responsible for the constitutively production of NO \[[@B33]\]. The inducible NOS (iNOS) is normally inactive in the vasculature \[[@B34]\], but its expression and activity can be induced in many cell types under oxidative and inflammatory stimuli; as a matter of fact several cytokines have been detected in the endothelium, in the media, and in the adventitia of blood vessels, as well as in neuronal cells and hepatocytes. Moreover, it is well known that NO produced by iNOS participates to the response of the immune system in killing bacteria and other exogeno