ENOS Uncoupling

Under physiologic conditions, NOS isoforms synthesize NO, which has a key role in vasodilation, antioxidation, and in mediation of vascular homeostasis. Under pathologic conditions, however, NOS isoforms can transform into prooxidants, generating superoxide rather than NO. This switch, which may involve constitutive eNOS and nNOS as well as the inducible NOS isoform (iNOS), is termed NOS uncoupling. NOS uncoupling refers to both the decreased NO-producing activity of the enzyme as well as its increased capacity to produce superoxide [23].

eNOS uncoupling is currently thought to play an important role in aging and cardiovascular diseases including diabetes mellitus, hypertension, hypercholester-olemia, atherosclerosis, cigarette smoking, and SCD [24]. Recent findings demonstrated that eNOS uncoupling in the penis is a significant contributor to oxidative stress and ED, as discussed later in this chapter.

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