Throughout the human gastrointestinal tract a variety of reactive nitrogen oxides are continuously formed as a result of a complex interplay between the host, commensal bacteria and dietary factors. These compounds include nitric oxide, nitrite, nitrate, peroxynitrite, S-nitrosothiols, nitrated fatty acids and N-nitrosamines, all of which are bioactive with the potential to affect physiological and pathological processes locally in the gut as well as systemically after absorption. Historically, the literature has been dominated by studies on the formation of potentially carcinogenic nitrosamines, but the focus was shifted in the 1980s with the seminal discovery of the L-arginine-nitric oxide pathway and its profound impact on normal physiological functions. More recently, a nitrate-nitrite-nitric oxide pathway has been discovered, with implications for local host defence and gut mucosal integrity and, intriguingly, also for systemic regulation of cardiovascular and metabolic function. This review discusses recent advances in the understanding of the formation, biochemistry, physiology and pathophysiology of reactive nitrogen oxides in the gastrointestinal tract. In addition, opportunities for nitric oxide-based pharmacological or dietary interventions are highlighted.
- Nitric oxide
- inflammatory bowel disease
- gastric ulcer
- nitro fatty acids
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Funding Generous support was received from the Swedish Research Council, Torsten and Ragnar Söderberg Foundation, Vinnova (CIDaT), the EU 7th Framework Program (Flaviola) and Karolinska Institutet. The authors acknowledge the funding agencies in the paper which refer to the original papers described in the review.
Competing interests JOL and EW are named co-inventors on pending patent applications related to the pharmacological use of nitrate and nitrite salts.
Provenance and peer review Commissioned; externally peer reviewed.