The antimicrobial activity of nitric oxide and related nitrogen intermediates
Endogenous production of nitrate in patients with infective gastroenteritis is increased manifold, and this increase originates from endogenous production of nitric oxide via the enzymatic L-arginine-NO pathway. Endogenous nitrate production seems to be a specific feature of infective gastroenteritis; no significant increase is observed in non-infective diarrhoeal conditions, and the production during other infective conditions such as septicaemia is comparatively modest. Twenty four hours urinary nitrate excretion after a period of minimal oral nitrate intake is the golden standard for measuring endogenous nitrate production, but is difficult to implement and prone to sampling errors. The urinary nitrate/creatinine ratio appears a satisfactory alternative provided that a standardised collection procedure is carried out. The urinary ratio reveals differences in endogenous nitrate production that remain undisclosed with serum nitrate measurements. Addition of nitrite achieves kill of micro-organisms where acid alone allows growth to continue. The synergism in antimicrobial action of acid and nitrite is evident against common gut pathogens such as the Enterobacteriaceae, including E. coli 0157, but also against the stomach pathogen H pylori, normally very resistant to acid alone. The antibacterial action of acidified nitrite becomes apparent at physiological concentrations of acid and nitrite after exposure times that are within the passage time of a food bolus through the stomach. Acidified nitrite also has an antifungal effect against Candida albicans, however at concentrations of acid and nitrite not normally found in the human upper gastro-intestinal tract. The antimicrobial activity of acidified nitrite is enhanced by thiocyanate, also present in gastric juices. Ascorbic acid provides protection against the antibacterial action of acidified nitrite, suggesting that NO is not the antibacterial agent. Acidification of salivary nitrite in the stomach will increase host defence against ingested pathogens. Generation of salivary nitrite increases greatly after nitrate ingestion, suggesting that ingestion of foods rich in nitrate may protect against infective gastroenteritis.