Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats

Effects of dietary protein or arginine deficiency on constitutive and lipop olysaccharide (LPS)-induced nitric oxide (NO) synthesis were determined in young rats by quantifying urinary nitrate excretion. In Experiment 1, 30-d- old rats (n = 16)were divided randomly into two groups (n = 8/group) and pa ir-fed on the basis of body weight semipurified isocaloric diets containing 20 or 5% casein. In Experiment 2, 30-d-old rats (n = 24) were divided rand omly into three groups (n = 8) and pair-fed on the basis of body weight pur ified isonitrogenous and isocaloric diets (composed of amino acids) contain ing 0.0, 0.3 or 1.0% L-arginine. In both experiments, daily collection of u rine was initiated 10 d after the start of pair-feeding. On d 17 after the pair-feeding was initiated, LPS (1 mg/kg body wt) was injected intraperiton eally into rats, and urine was collected daily for an additional 7 d. In Ex periments 3 and 4, activities of constitutive and inducible NO synthases we re measured in macrophages and various tissues from protein- or arginine-de ficient rats (n = 6). Body weight was lower in rats fed the 5% casein diet or the 0.0 and 0.3% arginine diets than in those fed 20% casein or 1% argin ine, respectively. Dietary protein or arginine deficiency decreased serum c oncentrations of arginine and urinary nitrate excretion before and after LP S treatment, indicating impaired constitutive and inducible NO synthesis. P rotein malnutrition reduced constitutive and inducible NO synthase activiti es in brain, heart, jejunum, lung, skeletal muscle and spleen, and inducibl e NO synthase activity in macrophages. Because NO is a mediator of the immu ne response and is the endothelium-dependent relaxing factor, impaired NO s ynthesis may help explain immunodeficiency and cardiovascular dysfunction i n protein- or arginine-deficient subjects.