Mammalian nitrate biochemistry: metabolism and endogenous synthesis.

The metabolic fate of an oral dose of 3.5 mmol 15N-labelled nitrate was investigated in young adults. An average of 60% of the 15N-nitrate dose appeared in the urine within 48 h; less than 0.1% appeared in the faeces. Some of the 15N label of nitrate was found in the urine (3%) and faeces (0.2%) in the form of ammonia and urea; the remainder of the dose was attributed to nitrate loss via metabolism to other reduced nitrogen compounds. Studies with germ-free rats indicated that half of the nitrate metabolism is due to mammalian processes. These and previous studies show that not all of the nitrate excreted in the urine is of dietary origin but evolves from endogenous synthesis. An oral dose of 15N-ammonium acetate was incorporated into urinary 15N-nitrate in rats, suggesting that ammonia is a precursor of nitrate. Furthermore, Escherichia coli lipopolysaccharide was found to be a potent stimulus of nitrate excretion (nine-fold increase), due to an increased rate of synthesis. Two other types of experimentally induced inflammatory states - injection of carrageenan and of turpentine - enhanced nitrate synthesis. It is proposed that the pathway of nitrate biosynthesis may be the result of oxidation of reduced nitrogen compounds by oxygen radicals generated by an activated reticuloendothelial system.