"Repurposing" of Xanthine Oxidoreductase as a Nitrite Reductase: A New Paradigm for Therapeutic Targeting in Hypertension.

SIGNIFICANCE: In contrast to nitric oxide (NO), which has well-established, important effects in regulation of cardiovascular homeostasis, its oxidative metabolite nitrite has, until recently, been considered to be of minor functional significance. RECENT ADVANCES: However, this view of nitrite has been radically revised over the past 10 years with evidence now supporting a critical role for this anion as a storage form of NO. CRITICAL ISSUES: Importantly, while hypoxia and acidosis have been shown to play a pivotal role in the generation of nitrite to NO, a number of mammalian nitrite reductases have been identified that facilitate the reduction of nitrite. Critically, these nitrite reductases have been demonstrated to operate under physiological pH conditions and in normoxia, extending the functional remit of this anion from an ischemic mediator to an important regulator of physiology. One particular nitrite reductase that has been shown to operate under a wide range of environmental conditions is the enzyme xanthine oxidoreductase (XOR). FUTURE DIRECTIONS: In this review, we discuss the evidence supporting a role for XOR as a nitrite reductase while focusing particularly on its function in hypertension. In addition, we discuss the potential merit in exploiting this activity of XOR in the therapeutics of hypertension.