Whole-body synthesis of l-homoarginine in pigs and rats supplemented with l-arginine

Recent studies suggest an important role for l-homoarginine in cardiovascular, hepatic and neurological functions, as well as the regulation of glucose metabolism. However, little is known about whole-body l-homoarginine synthesis or its response to dietary l-arginine intake in animals. Four series of experiments were conducted to determine l-homoarginine synthesis and catabolism in pigs and rats. In Experiment 1, male and female pigs were fed a corn- and soybean meal-based diet supplemented with 0.0-2.42 % l-arginine-HCl. In Experiment 2, male and female rats were fed a casein-based diet, while receiving drinking water containing supplemental l-arginine-HCl to provide 0.0-3.6 g l-arginine/kg body-weight/day. In both experiments, urine collected from the animals for 24 h was analyzed for l-homoarginine and related metabolites. In Experiment 3, pigs and rats received a single oral dose of 1 or 10 mg l-homoarginine/kg body-weight, respectively, and their urine was collected for 24 h for analyses of l-homoarginine and related substances. In Experiment 4, slices of pig and rat tissues (including liver, brain, kidney, heart, and skeletal-muscle) were incubated for 1 h in Krebs-bicarbonate buffer containing 5 or 50 A mu M l-homoarginine. Our results indicated that: (a) animal tissues did not degrade L-homoarginine in the presence of physiological concentrations of other amino-acids; (b) 95-96 % of orally administered l-homoarginine was recovered in urine; (c) l-homoarginine was quantitatively a minor product of l-arginineg catabolism in the body; and (d) dietary l-arginine supplementation dose-dependently increased whole-body l-homoarginine synthesis. These novel findings provide a new framework for future studies of l-homoarginine metabolism and physiology in animals and humans.