Figure 3.

Effects of oxidative stress on normal endothelial nitric oxide synthase activity. Normal endothelial nitric oxide synthase (eNOS) activity involves the conversion of l-arginine to l-citrulline and nitric oxide (NO), with substrates nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen (O₂). Tetrahydrobiopterin (BH₄) is an important cofactor in this enzymatic reaction. Nitric oxide then diffuses to the vascular smooth muscle cell (SMC), resulting in vasodilation. Multiple risk factors lead to endothelial cell oxidative stress, which disrupts normal eNOS activity via eNOS uncoupling, superoxide production, peroxynitrate production, eNOS inhibition, decreased BH₄, and decreased NO bioavailability, which ultimately impairs endothelium-dependent vasodilation. Created with BioRender.com and published with permission.