Citrulline ingestion did not improve the age‐associated reduction in nitric oxide synthesis (698.6)

Abstract

A reduction in nitric oxide (NO) bioavailability that impairs peripheral blood flow regulation is a natural consequence of aging. Therefore, we investigated the effect of ingestion of citrulline, the precursor of arginine, on de novo arginine and NO synthesis at baseline and during citrulline ingestion. A total of 3g of citrulline was ingested every 15 min for 3 h. A 6‐h stable isotope infusion protocol was performed in young (n=8, 27 ± 1.1 y) and elderly subjects (n=8, 76.6 ± 3.1 y) using primed constant infusions of ring‐ L‐[guanidine‐15N2]arginine, L‐[ureido‐13C,5,5‐2H2]citrulline,and ring‐[2H5]phenylalanine. Basal NO synthesis [0.32 ± 0.03 vs. 0.47 ± 0.05 μmol/kg ffm/h; p < 0.02], but not de novo arginine [12.5 ± 1.60 vs. 16.4 ± 1.47 μmol/kg ffm/h], was significantly lower in the elderly vs. the young. Citrulline ingestion increased de novo arginine synthesis in both the elderly and the young, but to a greater extent in the young [55.4 ± 9.64 vs. 72.3 ± 5.96 μmol/kg ffm/h; p < 0.01]. Citrulline ingestion increased NO synthesis in the young [3.47 ± 0.65 μmol/kg ffm/h; p < 0.01], but not in the elderly [1.26 ± 0.42 μmol/kg ffm/h; p = 0.08]. We conclude that aging reduces NO synthesis. This decrease in NO synthesis cannot be attributed to limited availability of citrulline but to the inability to synthesize NO via NOS.Grant Funding Source: NIH/NIA P30 AG028718