title: Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise.
abstract: Age-dependent alterations of the vessel wall may predispose older individuals to increased cardiovascular pathology. Aging is associated with an impaired bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity under fasting conditions and is an important storage pool of NO. To test the hypothesis that aging is associated with an impaired capacity of the vasculature to increase plasma nitrite during exercise, 29 young and 28 old healthy individuals (25 +/- 1 years and 58 +/- 2 years; P < 0.001) without major cardiovascular risk factors were enrolled. Exercise stress was similar in both groups. Baseline nitrite did not differ (107 +/- 8 vs. 82 +/- 10 nmol/l, young vs. old; n.s.) although a trend toward higher nitrite levels in young individuals was seen. In young subjects, exercise increased plasma nitrite by 38 +/- 7% (P < 0.001) compared to only 13 +/- 8% (P = n.s.) in older subjects. L-NMMA blocked increases of nitrite. Endothelial function, as defined by flow-mediated-dilation (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4 +/- 0.4% vs. 6.7 +/- 0.3%; P < 0.01). Multivariate analysis showed that age (P = 0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of nitrite increase. The fact that aging is associated with an impaired capacity of the vasculature to adequately increase nitrite to physiological stimuli may contribute to attenuated maintenance and further deterioration of vascular homeostasis with aging.
authors.affiliation: Dept. of Medicine, Pulmonology and Vascular Medicine, University Hospital Aachen, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Jan
authors.initials: J
authors.lastname: Balzer
authors.forename: Eva
authors.initials: E
authors.lastname: Kehmeier
authors.forename: Sarah
authors.initials: S
authors.lastname: Mangold
authors.forename: Thorsten
authors.initials: T
authors.lastname: Leyendecker
authors.forename: Jessica
authors.initials: J
authors.lastname: Rottler
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Marc W
authors.initials: MW
authors.lastname: Merx
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001916:Brachial Artery / Q000378:metabolism / Q000503:physiopathology; D008078:Cholesterol, LDL / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000097:blood*; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase