Oral administration of L‐leucine reduces nitric oxide synthesis by endothelial cells of rats

Abstract

High concentrations of branched‐chain amino acids in plasma are commonly associated with endothelial dysfunction in obese humans and animals. This study tested the hypothesis that elevated levels of leucine in plasma can reduce nitric oxide (NO) synthesis by endothelial cells (EC). Beginning at 19 weeks of age, male Sprague‐Dawley rats were fed a semi‐purified diet containing a normal fat content and received drinking water containing either 1% L‐leucine or 0.68% L‐alanine (isonitrogenous control) (n=8/group). Twenty‐four‐hour whole‐body energy expenditure of rats was determined every 4 weeks using Oxymas (an open circuit calorimeter, Columbus Instruments, Ohio). At 31 weeks of age, rats were euthanized to obtain tissues. Oral administration of leucine increased (P < 0.01) concentrations of leucine in plasma by 35%, but did not affect (P > 0.05) water consumption (25 mL/kg BW per day), food intake, body weight, skeletal muscle weight, white adipose tissue weight, or whole‐body heat production. Leucine administration enhanced (P < 0.05) glutamine:fructose‐6‐phosphate transaminase activity and decreased (P < 0.05) NO synthesis in EC and whole‐body insulin sensitivity. These novel results indicate that elevated concentrations of leucine promote glucosamine synthesis and reduce NO production by EC, contributing to increased risk for cardiovascular disease. (Supported by AHA and NIH grants).