Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress

Figure 3

Endothelial dysfunction due to oxidative stress. The image shows how vascular oxidative stress leads to endothelial dysfunction. (a) represents the production of nitric oxide (NO) from L-arginine by endothelial nitric oxide synthase (eNOS) in a healthy endothelium, where levels of superoxide anion (O₂⁻) are low. NO diffuses from the endothelium to the vascular smooth muscle, where it activates soluble guanylate cyclase (sGC), which increases the levels of guanosine 3,5 cyclic monophosphate (cGMP), thus leading to vasodilation. (b) represents acute vascular oxidative stress, with an increase in O₂⁻ production, followed by an increase in peroxynitrite (ONOO⁻) levels. ONOO⁻ produces endothelial dysfunction by directly reducing the NO available for activating sGC and by reducing prostaglandin I₂ (PGI₂) content via nitration PGI₂ synthase. If oxidative stress is persistent (c), eNOS becomes uncoupled, producing O₂⁻ instead of NO and aggravating endothelial dysfunction.

(a) Healthy endothelium

(b) Acute oxidative stress

(c) Persistent oxidative stress