Evidence map›Paper›PMID 22500004›Full record

ArticleJournal of applied physiology (Bethesda, Md. : 1985)2012

Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin.

Rebecca S Bruning, Lakshmi Santhanam, Anna E Stanhewicz, Caroline J Smith, Dan E Berkowitz, W Larry Kenney, Lacy A Holowatz

Open access · greenAbstract read
In one paragraph

Article in Journal of applied physiology (Bethesda, Md. : 1985), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

68 citing papers in PubMed, 120 citations in OpenAlex.

  1. Trial
  2. ETAmerican journal of physiology. Heart and circulatory physiology · 2021
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  14. Sex differences in heat stress vulnerability among middle-aged and older adults (PSU HEAT Project).American journal of physiology. Regulatory, integrative and comparative physiology · 2024
    Article
  15. Article
  16. Article
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  18. Within-limb variation in skin pigmentation does not influence cutaneous vasodilation.Journal of applied physiology (Bethesda, Md. : 1985) · 2023
    Article
  19. Combining hypoxia with thermal stimuli in humans: physiological responses and potential sex differences.American journal of physiology. Regulatory, integrative and comparative physiology · 2023
    Review
  20. Article

8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Rebecca S BruningDepartment of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Lakshmi Santhanam
Anna E Stanhewicz
Caroline J Smith
Dan E Berkowitz
W Larry Kenney
Lacy A Holowatz
Pennsylvania State University · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Penn State Clinical and Translational Science InstituteUL1TR000127 · NCATS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SINOWAY, LAWRENCE I · 2012 to 2015
$17.1M
Age and Control of Human Skin FlowR01AG007004 · NIA · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI KENNEY, W. LARRY · 1994 to 2013
$4.9M
Essential Hypertension & Human Skin Blood FlowR01HL093238 · NHLBI · PENNSYLVANIA STATE UNIVERSITY, THE · PI ALEXANDER, LACY M. · 2009 to 2018
$4.3M
NCATS NIH HHS UL1 TR000127NHLBI NIH HHS R01 HL093238NHLBI NIH HHS R01-HL-093238-02NIA NIH HHS R01 AG007004
6 · The paper itself

Abstract

Local skin heating is used to assess microvascular function in clinical populations because NO is required for full expression of the response; however, controversy exists as to the precise NO synthase (NOS) isoform producing NO. Human aging is associated with attenuated cutaneous vasodilation but little is known about the middle aged, an age cohort used for comparison with clinical populations. We hypothesized that endothelial NOS (eNOS) is the primary isoform mediating NO production during local heating, and eNOS-dependent vasodilation would be reduced in middle-aged skin. Vasodilation was induced by local heating (42°C) and during acetylcholine dose-response (ACh-DR: 0.01, 0.1, 1.0, 5.0, 10.0, 50.0, 100.0 mmol/l) protocols. Four microdialysis fibers were placed in the skin of 24 men and women; age cohorts were 12 middle-aged (53 ± 1 yr) and 12 young (23 ± 1 yr). Sites served as control, nonselective NOS inhibited [N(G)-nitro-l-arginine methyl ester (l-NAME)], inducible NOS (iNOS) inhibited (1400W), and neuronal NOS (nNOS) inhibited (N(ω)-propyl-l-arginine). After full expression of the local heating response, l-NAME was perfused at all sites. Cutaneous vascular conductance was measured and normalized to maximum (%CVC(max): Nitropress). l-NAME reduced %CVCmax at baseline, all phases of the local heating response, and at all ACh concentrations compared with all other sites. iNOS inhibition reduced the initial peak (53 ± 2 vs. 60 ± 2%CVC(max); P < 0.001); however, there were no other differences between control, nNOS-, and iNOS-inhibited sites during the phases of local heating or ACh-DR. When age cohorts were compared, NO-dependent vasodilation during local heating (52 ± 6 vs. 68 ± 4%CVC(max); P = 0.013) and ACh perfusion (50 mmol/l: 83 ± 3 vs. 93 ± 2%CVC(max); 100 mmol/l: 83 ± 4 vs. 92 ± 3%CVC(max); both P = 0.03) were reduced in middle-aged skin. There were no differences in NOS isoform expression obtained from skin biopsy samples between groups (all P > 0.05). These data suggest that eNOS mediates the production of NO during local heating and that cutaneous vasodilation is attenuated in middle-aged skin.

Indexed as

AcetylcholineAdultCohort StudiesFemaleHeatingHumansMaleMicrodialysisMiddle AgedNitric OxideNitric Oxide Synthase Type IIIProtein IsoformsSkinSkin Physiological PhenomenaVasodilationYoung AdultAcetylcholineNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanProtein Isoforms

Identifiers

PMID22500004
PMCPMC3378394
OpenAlexW2009268899

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.