Studies on the metabolism of amino acids and related compounds in vivo. IV. Blood ammonia and urea levels following intraperitoneal administration of amino acids and ammonium acetate, and the effect of arginine thereon

Abstract

Blood ammonia and urea levels were determined in rats which had been injected intraperitoneally (a) with LD 99.9 ammonium acetate alone and with a prior injection of l-arginine. HCl, l-ornithine. HCl, or l-citrulline; (b) with LD 99.9 levels of l- or d-amino acids; (c) with LD 99.9 levels of l-amino acids together with l-arginine · HCl; and (d) with an LD 99.9 level of a mixture of nine essential l-amino acids in the presence and absence of l-arginine. HCl. 1. ( a). Injection of an LD 99.9 dose of ammonium acetate was followed by a rapid rise in blood ammonia, a moderate increase in blood urea, and death of the animals; in the presence of protective levels of arginine, ornithine, or citrulline, the rise in blood ammonia was quickly checked and the values of this component rapidly fell to normal levels as the urea markedly increased, and the animals survived. 2. ( b). Animals injected with LD 99.9 levels of l- and d-amino acids died with elevated blood ammonia, and with elevated blood urea except for l-valine, and l- and d-histidine. HCl which evoked normal blood urea levels. 3. ( c). Addition of l-arginine. HCl to each of the l-amino acids, resulted in survival of the threonine-injected rats, a drop in the blood ammonia levels of rats given isoleucine, leucine, threonine, lysine, and tryptophan, with no change in the blood ammonia levels of rats given methionine, valine, histidine. HCl, and phenylalanine; the blood urea levels in animals injected with isoleucine, leucine, threonine, and phenylalanine appreciably increased, whereas with the five other amino acids no change in urea levels was noted. 4. ( d). Animals given the LD 99.9 mixture of nine essential l-amino acids died with a moderately elevated blood ammonia and a slightly subnormal blood urea level. In the presence of a relatively low level of l-arginine. HCl the animals survived with a normal level of blood ammonia and an elevated urea level. In the presence of a much higher level of l-arginine. HCl, the animals died with elevated blood ammonia and urea levels, the innate toxic effect of so much arginine outweighing its ordinary protective effect.