Figure 3.

eNOS is activated by an increase in Ca²⁺ levels, which recruits CaM and Hsp90 to the enzyme, prompting caveolae (Cav-1) to dissociate from eNOS [60]. The activity of CaM and Hsp90 is promoted by EGF, which promotes CaM expression and the recruitment of Hsp90 [60]. The eNOS complex can then be activated by the phosphorylation of eNOS, which occurs via PKA (activated by shear stress), VEGF (via Ser/Thr kinase Akt), insulin, and bradykinin, which is regulated by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) [60]. These stimuli result in the dissociation of adenylate cyclase (Ac) from eNOS. The eNOS complex can then catalyze the production of l-citrulline and NO from l-arginine, and thus increase NO generation.