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Cited by 68Cardiovascular Syncope and Autonomic DisordersNitric Oxide and Endothelin EffectsHeart Rate Variability and Autonomic Control

Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome

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Stewart, Julian M., Medow, Marvin S., Minson, Christopher T., Taneja, Indu·2007·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00600.2007PMC PMC4511496
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Abstract

Low flow postural tachycardia syndrome (POTS), is associated with reduced nitric oxide (NO) activity assumed to be of endothelial origin. We tested the hypothesis that cutaneous microvascular neuronal NO (nNO) is impaired, rather than endothelial NO (eNO), in POTS. We performed three sets of experiments on subjects aged 22.5 ± 2 yr. We used laser-Doppler flowmetry response to sequentially increase acetylcholine (ACh) doses and the local cutaneous heating response of the calf as bioassays for NO. During local heating we showed that when the selective neuronal nNO synthase (nNOS) inhibitor N ω-nitro-l-arginine-2,4-l-diaminobutyric amide ( N ω, 10 mM) was delivered by intradermal microdialysis, cutaneous vascular conductance (CVC) decreased by an amount equivalent to the largest reduction produced by the nonselective NO synthase (NOS) inhibitor nitro-l-arginine (NLA, 10 mM). We demonstrated that the response to ACh was minimally attenuated by nNOS blockade using N ω but markedly attenuated by NLA, indicating that eNO largely comprises the receptor-mediated NO release by ACh. We further demonstrated that the ACh dose response was minimally reduced, whereas local heat-mediated NO-dependent responses were markedly reduced in POTS compared with control subjects. This is consistent with intact endothelial function and reduced NO of neuronal origin in POTS. The local heating response was highly attenuated in POTS [60 ± 6 percent maximum CVC(%CVC max)] compared with control (90 ± 4 %CVC max), but the plateau response decreased to the same level with nNOS inhibition (50 ± 3 %CVC max in POTS compared with 47 ± 2 %CVC max), indicating reduced nNO bioavailability in POTS patients. The data suggest that nNO activity but not NO of endothelial NOS origin is reduced in low-flow POTS.

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  • Acrocyanosis in POTS is not due to increased venous compliance but may be caused by decreased skin blood flow, possibly related to abnormal cutaneous nitric oxide activity.

    “This acrocyanosis in POTS is not due to increased venous compliance [22;23] but may be caused by a decrease in blood flow to the skin, possibly related to abnormal cutaneous nitric oxide activity [24].”

    From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [24]

  • Neuronal nitric oxide synthase, and not endothelial nitric oxide synthase, was determined to be responsible for causing this phenomenon.

    “Neuronal nitrous oxide synthase, and not endothelial nitrous oxide synthase, was determined to be responsible for causing this phenomenon (29).”

    From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [29]

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Authors
Stewart, J. M., Medow, M. S., Minson, C. T., & Taneja, I.
Affiliations
New York Medical College (US)
ORCID
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2007-10
Volume
293
Issue
4
Pages
H2161-H2167
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.00600.2007
PMC
PMC4511496
OpenAlex
W2103260468
Cited by
68
References
57
Citations by year
2025: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 7 · 2013: 4 · 2012: 4
FWCI
7.30
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL087803, R01HL074873, 5R01-HL-74873)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK071647)
Topics
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
postural orthostatic tachycardia syndrome, neuronal nitric oxide, cutaneous microvascular function, nNOS inhibition, endothelial nitric oxide, acetylcholine response, cutaneous vascular conductance, nitric oxide bioavailability, intradermal microdialysis
MeSH terms
Acetylcholine, Adolescent, Adult, Blood Flow Velocity, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme Inhibitors, Female, Hot Temperature, Humans, Microcirculation, Neurons, Nitric Oxide, Posture, Regional Blood Flow, Research Design, Skin, Syndrome, Tachycardia, Vasodilator Agents, Case-Control Studies, Laser-Doppler Flowmetry, Nitroarginine, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type III

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