Dietary Nitrite in Nitric Oxide Biology: A Redox Interplay with Implications for Pathophysiology and Therapeutics

Barbara      S. Rocha; Bruno      Gago; Cassilda      Pereira; Rui      M. Barbosa; Silvina      Bartesaghi; Jon      O. Lundberg; Rafael      Radi; Joao      Laranjinha

Abstract

Until recently, nitrite has been considered a stable and inert metabolite of nitric oxide ( • NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to • NO and thus one may consider a reversible interaction regarding ˙NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest ˙NO reservoir in the body. This notion has obvious importance when considering that ˙NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages-containing polyphenols, a rich chemistry occurs in which ˙NO, ˙NO-derived species and nitroso or nitrated derivatives may be formed. Most of these molecules may play an important role in vivo. For instance, it has been shown that polyphenol-catalyzed nitrite reduction to ˙NO may induce local vasodilation and that ethanol (from wine) reacts with ˙NO-derived species yielding nitroso derivatives endowed with ˙NO-donating properties. Thus, this review reveals new pathways for the biological effects of dietary nitrite encompassing its interaction with dietary components (polyphenols, red wine, lipids), yielding products with impact on human physiology and pathology, namely cardiovascular, urinary and gastrointestinal systems. Novel therapeutic strategies are therefore expected to follow the elucidation of the mechanisms of nitrite biology.

Keywords: Nitric oxide, nitrite, stomach, polyphenols, ethylnitrite, EDRF, Veillonella atypica, Veillonella dispar