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Scheme showing immediate causes and effects of NOS uncoupling. Decreases in the NOS substrate L-Arg or cofactor tetrahydrobiopterin (BH4) results in decreases in NO and increases in superoxide (O2˙− ). The O2˙− reacts rapidly with NO to form the highly reactive nitrogen species peroxynitrite (ONOO ). This further decreases bioavailability of NO for downstream signaling events.
