{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:02:46Z","timestamp":1792785766221,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Texas A&M University funds","id":[{"id":"https:\/\/ror.org\/01f5ytq51","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Arginine, as precursor of the antihypertensive metabolite nitric oxide, may influence blood pressure (BP) regulation and is therefore linked to hypertension, a serious global health issue. Thus, we investigated whether hypertension relates to alterations in arginine metabolism and examined the role of biological sex and body composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We stratified 762 older adults (50-95 years old) participating in the MEDIT-trial into 4 BP groups (normal, elevated, stage 1 and 2 hypertension) per 2025 ACC\/AHA guidelines. Body composition was assessed by dual-energy X-ray absorptiometry. After administering stable tracers of arginine, citrulline, and ornithine, blood samples were taken to measure postabsorptive plasma amino acid concentrations and tracer enrichments by LC-MS\/MS. Compartmental modeling was applied to determine amino acid kinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Age and glucose, hs-CRP, and arginine levels were comparable across groups. Older adults with stage 1 and stage 2 hypertension had higher BMIs than those with normal BP (29.7 kg\/m2 and 31.0 kg\/m2 vs. 27.8 kg\/m2). Whole-body and intracellular arginine production in stage 2 hypertension were increased by 10.4% and 10.7% compared to those with normotension (all: P\u2009&amp;lt;\u2009.05), particularly in females (whole-body: +13.7%; intracellular: +18.3%; all: P\u2009&amp;lt;\u2009.02). While females showed progressive increases in body composition parameters along BP groups, males displayed relatively stable values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Arginine metabolism in older adults is influenced by hypertension severity, with sex-specific differences in metabolic adaptation. Further research is warranted determining whether hypertension treatment for older adults should be individualized to disease severity, accounting for the upregulated arginine metabolism and sex-specific differences, which may lead to improved outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>www.clinicalTrials.gov, Trial Numbers: NCT01787682, NCT01871350, NCT01624792, NCT01890824, NCT02082418, NCT02157844, NCT06801964, NCT02065141, NCT03159390, NCT02770092, NCT02908425, NCT02780219, NCT02780206, NCT03327181, NCT06801951, NCT03796455, NCT04928872, NCT04461236, NCT05395390, NCT05240885, NCT06628349.<\/jats:p>\n                  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