Trial reportAmerican journal of physiology. Regulatory, integrative and comparative physiology2011
Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants.
Trial report in American journal of physiology. Regulatory, integrative and comparative physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Salsalate negatively impacts microvascular function in women with endometriosis.American journal of physiology. Heart and circulatory physiology · 2025Trial
- Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Trial
- Acute localized administration of tetrahydrobiopterin and chronic systemic atorvastatin treatment restore cutaneous microvascular function in hypercholesterolaemic humans.The Journal of physiology · 2011Trial
- Spectral changes in skin blood flow during pressure manipulations or sympathetic stimulation.Experimental physiology · 2024Article
- Climate change and the prevention of cardiovascular disease.American journal of preventive cardiology · 2022Review
- Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis.Microvascular research · 2022Article
- Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.The Journal of physiology · 2019Article
- Effect of statins on the association between high temperature and all-cause mortality in a socioeconomically disadvantaged population: a cohort study.Scientific reports · 2019Article
- Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation.American journal of physiology. Heart and circulatory physiology · 2018Article
- Fluid replacement modulates oxidative stress- but not nitric oxide-mediated cutaneous vasodilation and sweating during prolonged exercise in the heat.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- Edward F. Adolph Distinguished Lecture: Skin-deep insights into vascular aging.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Review
- Acute dairy milk ingestion does not improve nitric oxide-dependent vasodilation in the cutaneous microcirculation.The British journal of nutrition · 2016Article
- Altered skin flowmotion in hypertensive humans.Microvascular research · 2015Article
- Nonuniform, age-related decrements in regional sweating and skin blood flow.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- Tetrahydrobiopterin increases NO-dependent vasodilation in hypercholesterolemic human skin through eNOS-coupling mechanisms.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations.Microvascular research · 2013Article
- Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
- Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVC(max), P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVC(max), P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVC(max), P < 0.001) or combined with arginase inhibition (96 ± 3% CVC(max), P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVC(max), both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVC(max), P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVC(max,) P > 0.05) or combined with arginase inhibition (67 ± 4% CVC(max,) P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.