title: Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.
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 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 ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 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.
authors.affiliation: Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, iykim@uams.edu.
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Schutzler
authors.affiliation: College of Medicine Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
authors.forename: Amy
authors.initials: A
authors.lastname: Schrader
authors.affiliation: College of Medicine Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
authors.forename: Horace J
authors.initials: HJ
authors.lastname: Spencer
authors.affiliation: Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Gohar
authors.initials: G
authors.lastname: Azhar
authors.affiliation: Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas.
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
authors.affiliation: Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Wolfe
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000097:blood / Q000378:metabolism; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002956:Citrulline / Q000009:adverse effects / Q000627:therapeutic use*; D019587:Dietary Supplements / Q000009:adverse effects; D058620:Elder Nutritional Physiological Phenomena; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005542:Forearm; D006333:Heart Failure / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006940:Hyperemia / Q000209:etiology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D012039:Regional Blood Flow; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine
keywords: aging; arginine; endothelial dysfunction; stable isotope tracers