Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was similar to 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citruiline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 +/- 0.83 to 35.40 +/- 4.90 mu mol.kg body wt(-1).h(-1)] and to a greater extent in young adults (12.02 +/- 1.01 to 66.26 +/- 4.79 timollg body wt(-1).h(-1)). NO synthesis rate increased correspondingly in older (0.17 +/- 0.01 to 2.12 +/- 0.36 (mu mol.kg body wt(-1).h(-1)) and to a greater extent in young adults (0.36 +/- 0.04 to 3.57 +/- 0.47 p.moFkg body wt(-1).h(-1)). Consistent with the kinetic data. RH-FBF in the fasted state was similar to 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.