Evidence map›Paper›PMID 20558755›Full record

Trial reportJournal of applied physiology (Bethesda, Md. : 1985)2010

Roles of nitric oxide synthase and cyclooxygenase in leg vasodilation and oxygen consumption during prolonged low-intensity exercise in untrained humans.

William G Schrage, Brad W Wilkins, Christopher P Johnson, John H Eisenach, Jacqueline K Limberg, Niki M Dietz, Timothy B Curry, Michael J Joyner

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of applied physiology (Bethesda, Md. : 1985), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
11.6field-weighted citation impact, top 2% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

  1. Trial
  2. Increased cGMP improves microvascular exercise training adaptations in diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025
    Article
  3. Cyclooxygenase inhibition does not blunt thermal hyperemia in skeletal muscle of humans.Journal of applied physiology (Bethesda, Md. : 1985) · 2024
    Article
  4. Article
  5. Effect of histamine-receptor antagonism on leg blood flow during exercise.Journal of applied physiology (Bethesda, Md. : 1985) · 2020
    Article
  6. Review
  7. Article
  8. Review
  9. Comparison of the vasodilatory effects of sodium nitroprusside vs. nitroglycerin.Journal of applied physiology (Bethesda, Md. : 1985) · 2017
    Article
  10. Effects of chronic nitric oxide synthase inhibition on V'ONaunyn-Schmiedeberg's archives of pharmacology · 2017
    Article
  11. Review
  12. Skeletal muscle vasodilation during systemic hypoxia in humans.Journal of applied physiology (Bethesda, Md. : 1985) · 2016
    Review
  13. Article
  14. Review
  15. Article
  16. Thin-beam ultrasound overestimation of blood flow: how wide is your beam?Journal of applied physiology (Bethesda, Md. : 1985) · 2014
    Article
  17. Article
  18. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment.American journal of physiology. Regulatory, integrative and comparative physiology · 2013
    Article
  19. Review
  20. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia.American journal of physiology. Regulatory, integrative and comparative physiology · 2013
    Article
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

8 authors at 2 institutions in 1 country.

William G SchrageDepartment of Anesthesiology, Mayo Clinic, Rochester, MN, USA. wschrage@education.wisc.edu
Brad W Wilkins
Christopher P Johnson
John H Eisenach
Jacqueline K Limberg
Niki M Dietz
Timothy B Curry
Michael J Joyner
Mayo Clinic · USUniversity of Wisconsin–Madison · US

Funding

MAYO CLINIC CENTER FOR TRANSLATIONAL SCIENCE ACTIVITIESUL1RR024150 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$66.4M
PERFUSION OF ACTIVE MUSCLES--METABOLITES AND NERVESR01HL046493 · NHLBI · MAYO CLINIC ROCHESTER · PI JOYNER, MICHAEL J · 1997 to 2011
$3.7M
Beta-2 Receptor Polymorphisms and Vasodilation in HumansK23RR017520 · NCRR · MAYO CLINIC ROCHESTER · PI EISENACH, JOHN H · 2003 to 2007
$601k
Aging and Microvascular Dysfunction in Human Skeletal MuscleR21HL091397 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI SCHRAGE, WILLIAM G · 2009 to 2010
$388k
O2 Delivery and Functional Sympatholysis in Human MuscleF32HL078019 · NHLBI · MAYO CLINIC ROCHESTER · PI WILKINS, BRADLEY W · 2004 to 2006
$142k
PERFUSION OF ACTIVE MUSCLES: METABOLITES AND NERVESR29HL046493 · NHLBI · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI JOYNER, MICHAEL J · 1992 to 1996
–
NCRR NIH HHS RR-017520NCRR NIH HHS RR-024150NHLBI NIH HHS HL-091397NHLBI NIH HHS HL-46493NHLBI NIH HHS HL-78019NHLBI NIH HHS L30 HL074824
6 · The paper itself

Abstract

The vasodilator signals regulating muscle blood flow during exercise are unclear. We tested the hypothesis that in young adults leg muscle vasodilation during steady-state exercise would be reduced independently by sequential pharmacological inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) with NG-nitro-L-arginine methyl ester (L-NAME) and ketorolac, respectively. We tested a second hypothesis that NOS and COX inhibition would increase leg oxygen consumption (VO2) based on the reported inhibition of mitochondrial respiration by nitric oxide. In 13 young adults, we measured heart rate (ECG), blood pressure (femoral venous and arterial catheters), blood gases, and venous oxygen saturation (indwelling femoral venous oximeter) during prolonged (25 min) steady-state dynamic knee extension exercise (60 kick/min, 19 W). Leg blood flow (LBF) was determined by Doppler ultrasound of the femoral artery. Whole body VO2 was measured, and leg VO2 was calculated from blood gases and LBF. Resting intra-arterial infusions of acetylcholine (ACh) and nitroprusside (NTP) tested inhibitor efficacy. Leg vascular conductance (LVC) to ACh was reduced up to 53±4% by L-NAME+ketorolac infusion, and the LVC responses to NTP were unaltered. Exercise increased LVC from 4±1 to 33.1±2 ml.min(-1).mmHg(-1) and tended to decrease after L-NAME infusion (31±2 ml.min(-1).mmHg(-1), P=0.09). With subsequent administration of ketorolac LVC decreased to 29.6±2 ml.min(-1).mmHg(-1) (P=0.02; n=9). While exercise continued, LVC returned to control values (33±2 ml.min(-1).mmHg(-1)) within 3 min, suggesting involvement of additional vasodilator mechanisms. In four additional subjects, LVC tended to decrease with L-NAME infusion alone (P=0.08) but did not demonstrate the transient recovery. Whole body and leg VO2 increased with exercise but were not altered by L-NAME or L-NAME+ketorolac. These data indicate a modest role for NOS- and COX-mediated vasodilation in the leg of exercising humans during prolonged steady-state exercise, which can be restored acutely. Furthermore, NOS and COX do not appear to influence muscle VO2 in untrained healthy young adults.

Indexed as

ExerciseOxygen ConsumptionVasodilationAcetylcholineAdultBlood PressureCatecholaminesCyclooxygenase InhibitorsEnzyme InhibitorsFemaleHeart RateHumansInfusions, Intra-ArterialKetorolacLower ExtremityMaleAcetylcholineCatecholaminesCyclooxygenase InhibitorsEnzyme InhibitorsKetorolacNG-Nitroarginine Methyl EsterNitric Oxide SynthaseNitroprussideOxygenProstaglandin-Endoperoxide SynthasesVasodilator Agents

Identifiers

PMID20558755
PMCPMC3774514
OpenAlexW2094290794

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.