Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Abstract

Nitric oxide synthase (NOS) inhibitors alleviate the adverse effects of nitric oxide (NO) overproduction that occurs during peritonitis, a clinical condition that is accompanied by arginine deficiency. However, the variations in the disease severity and the dosage, route, and period of NOS inhibitor administration are debatable. Therefore, we investigated the dose effects of chronically infused NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on the anabolism, inflammatory responses, and arginine metabolism in parenterally fed rats with cecal puncture-induced subacute peritonitis. Male Wistar rats were divided into 4 groups and were administered total parenteral nutrition solutions with 0, 5 (low dose), 25 (medium dose), or 50 (high dose) mg·kg(-1)·d(-1) of L-NAME for 7 d. Sham-operated rats administered total parenteral nutrition solution and normal healthy rats fed chow diet were also included. Our results showed that parenteral infusion significantly decreased body weight gain and plasma citrulline concentrations. In rats with subacute peritonitis, the parenteral infusion-induced increases in circulating white blood cells and NO were significantly decreased, whereas the decrease in serum albumin levels was significantly increased. Rats with subacute peritonitis that were administered chronic infusion of L-NAME had a significantly reduced nitrogen balance. In addition, rats administered the medium dose of L-NAME had significantly increased plasma arginine, ornithine, glutamate, and proline. In conclusion, chronic infusion of NOS inhibitors may not alter systemic NO homeostasis and inflammatory response but may facilitate the production of arginine-associated amino acids and nitrogen excretion in cases of subacute peritonitis.