Urea cycle intermediate kinetics and nitrate excretion at normal and "therapeutic" intakes of arginine in humans

Abstract

We investigated the effects of a high dietary supplement of arginine on plasma arginine, ornithine, and leucine kinetics and on urea production and excretion in five healthy young adult men. Subjects received either 56 or 561 mg arginine.kg-1.day-1 for 6 days via a complete L-amino acid diet, and on day 7 a tracer protocol (first 3 h fasted; next 5 h fed) was conducted, involving primed constant intragastric infusions of L-[15N2-guanidino,5,5-2H2]arginine, L-[5-13C]ornithine, L-[5,5,5-2H3]leucine, and [15N2]urea, with a prime of H13CO3. Plasma arginine and ornithine fluxes increased significantly (P < 0.05) with arginine supplementation, as did the rate of conversion of plasma labeled arginine to ornithine (P < 0.05) and rate of ornithine oxidation (P < 0.001). However, absolute changes in ornithine kinetics were less than those for arginine or those based on changes expected from the change in arginine intake, implying a complex compartmentation in both whole body arginine and ornithine metabolism. The plasma NO3 concentration, daily output of total NO3, and conversion of [15N]arginine to NO3 did not differ between the diets. Urea production and excretion were reduced significantly with arginine supplementation, suggesting an anabolic effect on the whole body nitrogen economy, possibly via the raised plasma insulin levels (P = 0.013) during the prandial phase.