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Cited by 129Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionEicosanoids and Hypertension Pharmacology

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Neuronal Nitric Oxide Synthase Regulates Basal Microvascular Tone in Humans In Vivo

Seddon, Michael D., Chowienczyk, Philip J., Brett, Sally E., Casadei, Barbara, Shah, Ajay M.·2008·Circulation
DOI 10.1161/circulationaha.107.744540
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Abstract

Background— Nitric oxide (NO) has a pivotal role in the regulation of vascular tone and blood flow, with dysfunctional release contributing to disease pathophysiology. These effects have been attributed to NO production by the endothelial NO synthase (eNOS); however, recent evidence suggests that a neuronal NO synthase (nNOS) may also be expressed in arterial vessels. Methods and Results— We undertook a first-in-humans investigation of the role of nNOS in the local regulation of vascular blood flow in healthy subjects. Brachial artery infusion of the nNOS-specific inhibitor S -methyl- l -thiocitrulline (SMTC, 0.025 μmol/min to 0.2 μmol/min) caused a dose-dependent reduction in basal flow, with a 30.1±3.8% decrease at the highest dose (n=10; mean±SE; P <0.01). The effect of SMTC was abolished by coinfusion of the NO synthase substrate l -arginine but was unaffected by d -arginine. A similar reduction in basal flow with the nonselective NO synthase inhibitor N G -monomethyl- l -arginine (L-NMMA; 37.4±3.1%, n=10) required a 20-fold higher dose of 4 μmol/min. At doses that produced comparable reductions in basal flow, only L-NMMA (4 μmol/min) and not SMTC (0.2 μmol/min) inhibited acetylcholine-induced vasodilation; however, both SMTC and L-NMMA inhibited the forearm vasodilator response to mental stress. Conclusions— Basal forearm blood flow in humans is regulated by nNOS-derived NO, in contrast to the acetylcholine-stimulated increase in blood flow, which, as shown previously, is mediated primarily by eNOS. These data indicate that vascular nNOS has a distinct local role in the physiological regulation of human microvascular tone in vivo.

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  1. 10.1161/circ.104.2.191 · DOI
  2. 10.1161/circ.99.9.1156 · DOI
  3. 10.1161/circ.96.8.2542 · DOI

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Metadata

Authors
Seddon, M. D., Chowienczyk, P. J., Brett, S. E., Casadei, B., & Shah, A. M.
Affiliations
  • King's College London (GB)
  • From the Departments of Cardiology (M.D.S., A.M.S.) and Clinical Pharmacology (P.J.C., S.E.B.), Cardiovascular Division, King’s College London School of Medicine, London, United Kingdom; and Department of Cardiovascular Medicine (B.C.), University of Oxford, Oxford, United Kingdom.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-04-15
Volume
117
Issue
15
Pages
1991-1996
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.107.744540
OpenAlex
W1982282544
Cited by
129
References
23
Citations by year
2025: 5 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 1 · 2020: 8 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 5 · 2015: 13 · 2014: 8 · 2013: 13 · 2012: 11
FWCI
6.32
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Abbott Laboratories
  • National Institute for Health and Care Research
  • British Heart Foundation (PG/05/138/20014, CVH/99001)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
neuronal nitric oxide synthase, nitric oxide, microvascular tone, S-methyl-L-thiocitrulline, L-NMMA, L-arginine, acetylcholine-induced vasodilation, endothelial nitric oxide synthase, brachial artery infusion
MeSH terms
Acetylcholine, Adult, Arginine, Brachial Artery, Citrulline, Forearm, Humans, Male, Nitric Oxide, Stress, Psychological, Thiourea, Vasodilation, Vasomotor System, omega-N-Methylarginine, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type III

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