Suboptimal levels of BH4, or a decreased BH4/BH2 ratio, are significant contributors to eNOS uncoupling observed in hypertension, diabetes, and atherosclerosis (Vasquez-Vivar et al., 1998; Wever et al., 1997; Soltis and Cassis, 1991; Hong et al., 2001; Landmesser et al., 2003; Lee et al., 2009). Here, NOS3 is linked to hypertensive disorder.