Trial reportJournal of applied physiology (Bethesda, Md. : 1985)2013
Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms.
Trial report in Journal of applied physiology (Bethesda, Md. : 1985), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans.American journal of physiology. Heart and circulatory physiology · 2017Trial
- Impairments in central cardiovascular function contribute to attenuated reflex vasodilation in aged skin.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Trial
- Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms.Clinical science (London, England : 1979) · 2015Trial
- Oral sapropterin augments reflex vasoconstriction in aged human skin through noradrenergic mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2013Trial
- Reflex vasodilation and sweating in response to passive whole body heating are blunted in women with major depressive disorder.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease.International journal of molecular sciences · 2025Review
- Intermittent hand and forearm immersion in 20°C water attenuates thermal, cardiovascular, and perceptual strain in older adults during heat stress.Experimental physiology · 2025Article
- Sex differences in heat stress vulnerability among middle-aged and older adults (PSU HEAT Project).American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Comprehensive evaluation framework for intervention on health effects of ambient temperature.Eco-Environment & Health · 2024Review
- Experimental research in environmentally induced hyperthermic older persons: A systematic quantitative literature review mapping the available evidence.Temperature (Austin, Tex.) · 2024Article
- Heat stress vulnerability and critical environmental limits for older adults.Communications earth & environment · 2023Article
- Adverse heat-health outcomes and critical environmental limits (Pennsylvania State University Human Environmental Age Thresholds project).American journal of human biology : the official journal of the Human Biology Council · 2023Review
- Human temperature regulation under heat stress in health, disease, and injury.Physiological reviews · 2022Review
- Thermoregulatory reflex control of cutaneous vasodilation in healthy aging.Temperature (Austin, Tex.) · 2021Article
- Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.Experimental physiology · 2020Article
- Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.Alcoholism, clinical and experimental research · 2020Article
- Separate and combined effects of KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Folic acid supplementation does not attenuate thermoregulatory or cardiovascular strain of older adults exposed to extreme heat and humidity.Experimental physiology · 2018Article
- Edward F. Adolph Distinguished Lecture: Skin-deep insights into vascular aging.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. Acute, locally administered BH4 increases reflex vasodilation through NO-dependent mechanisms in aged skin. We hypothesized that oral sapropterin (Kuvan, shelf-stable pharmaceutical formulation of BH4) would augment reflex vasodilation in aged human skin during hyperthermia. Nine healthy human subjects (76 ± 1 yr) ingested sapropterin (10 mg/kg) or placebo in a randomized double-blind crossover design. Venous blood samples were collected prior to, and 3 h following, ingestion of sapropterin for measurement of plasma BH4. Three intradermal microdialysis fibers were placed in the forearm skin for local delivery of 1) lactated Ringer's solution, 2) 10 mM BH4, and 3) 20 mM N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced using a water-perfused suit. At 1°C rise in oral temperature, mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and expressed as a percentage of maximum (%CVCmax 28 mM sodium nitroprusside and local heat 43°C). Plasma concentrations of BH4 were significantly elevated 3 h after ingestion of sapropterin (0 h: 19.1 ± 2 pmol/ml vs. 3 h: 43.8 ± 3 pmol/ml; P < 0.001). Sapropterin increased NO-dependent vasodilation at control site (placebo: 14 ± 1 %CVCmax vs. sapropterin: 25 ± 4 %CVCmax; P = 0.004). Local BH4 administration increased NO-dependent vasodilation compared with control in placebo trials only (control: 14 ± 1 %CVCmax vs. BH4-treated: 24 ± 3 %CVCmax; P = 0.02). These data suggest oral sapropterin increases bioavailable BH4 in aged skin microvasculature sufficiently to increase NO synthesis through NOS and that sapropterin may be a viable intervention to increase skin blood flow during hyperthermia in healthy aged humans.
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