XDH and endothelial dysfunction: Importantly, in vitro, NH4 scavenged superoxide anion radicals created by the xanthine/xanthine oxidase reaction equipotent to BH4 but failed to modify acetylcholine-induced changes in forearm blood flow in chronic smokers in vivo, supporting the concept that, in addition to the reactive oxygen species burden of cigarette smoke, a dysfunctional eNOS due to BH4 depletion may contribute, at least in part, to endothelial dysfunction in chronic smokers [78].