Mammalian nitrate biosynthesis: incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment

Abstract

Incorporation of an oral dose of [15N]ammonium acetate into urinary [15N]nitrate has been demonstrated in the rat. Investigation of the regulation of nitrate synthesis has shown that Escherichia coli lipopolysaccharide potently stimulates urinary nitrate excretion (9-fold increase). It was further shown that the enhanced rate of nitrate excretion by lipopolysaccharide was due not to a reduction in nitrate metabolic loss but rather to an increased rate of synthesis. This conclusion was based on finding a proportionally increased incorporation of [15N]ammonium into nitrate nitrogen with lipopolysaccharide treatment. Nitrate biosynthesis was also increased by intraperitoneal injection of carrageenan and subcutaneous injection of turpentine. 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.