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Acute ingestion of citrulline stimulates nitric oxide synthesis in young and older subjects

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AJP Endocrinology and Metabolism

Published online on

Abstract

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 kinetics 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 weight (bw) was approximately 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3g) stimulated de novo arginine synthesis in both older [6.88±0.83 to 35.40±4.90 μmol/kg bw/h] and to a greater extent in young adults [12.02±1.01 to 66.26±4.79 μmol/kg bw/h]. NO synthesis rate increased correspondingly in older [0.17±0.01 to 2.12±0.36 μmol/kg bw/h] and to a greater extent in young adults [0.36±0.04 to 3.57±0.47 μmol/kg bw/h]. Consistent with the kinetic data, RH-FBF in the fasted state was approximately 40% reduced in older vs. young adults. However, citrulline ingestion (10g) 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 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.