Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance.
T Münzel, … , M M Tarpey, D G Harrison
T Münzel, … , M M Tarpey, D G Harrison
Published January 1, 1995
Citation Information: J Clin Invest. 1995;95(1):187-194. https://doi.org/10.1172/JCI117637.
View: Text | PDF
Research Article Article has an altmetric score of 9

Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance.

  • Text
  • PDF
Abstract

We sought to examine mechanisms underlying nitroglycerin (NTG) tolerance and "cross-tolerance" to other nitrovasodilators. Rabbits were treated for 3 d with NTG patches (0.4 mg/h) and their aortic segments studied in organ chambers. Relaxations were examined after preconstriction with phenylephrine. In NTG tolerant rabbit aorta, relaxations to cGMP-dependent vasodilators such as NTG (45 +/- 6%), SIN-1 (69 +/- 7%), and acetylcholine (ACh, 64 +/- 5%) were attenuated vs. controls, (90 +/- 2, 94 +/- 3, and 89 +/- 2% respectively, P < 0.05 for all), while responses to the cAMP-dependent vasodilator forskolin remained unchanged. In tolerant aorta, endothelial removal markedly enhanced relaxations to NTG and SIN-1 (82 +/- 4 and 95 +/- 3%, respectively). Other studies were performed to determine how the endothelium enhances tolerance. Vascular steady state .-O2 levels (assessed by lucigenin chemiluminescence) was increased twofold in tolerant vs. control vessels with endothelium (0.31 +/- 0.01 vs. 0.61 +/- 0.01 nmol/mg per minute). This difference was less in vessels after denudation of the endothelium. Diphenylene iodonium, an inhibitor of flavoprotein containing oxidases, and Tiron a direct .-O2 scavenger normalized .-O2 levels. In contrast, oxypurinol (1 mM) an inhibitor of xanthine oxidase, rotenone (50 microM) an inhibitor of mitochondrial electron transport and NG-nitro-L-arginine (100 microM) an inhibitor of nitric oxide synthase did not affect the chemiluminescence signals from NTG-tolerant aortas. Pretreatment of tolerant aorta with liposome-entrapped, pH sensitive superoxide dismutase (600 U/ml) significantly enhanced maximal relaxation in response to NTG, SIN-1, and ACh, and effectively reduced chemiluminescence signals. These studies show that continuous NTG treatment is associated with increased vascular .-O2-production and consequent inhibition of NO. mediated vasorelaxation produced by both exogenous and endogenous nitrovasodilators.

Authors

T Münzel, H Sayegh, B A Freeman, M M Tarpey, D G Harrison

×

Total citations by year

Year: 2025 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1991 1970 Total
Citations: 1 2 1 5 3 3 7 13 8 4 8 21 16 11 16 34 19 24 18 28 27 29 38 33 29 32 49 27 23 6 4 1 540
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2017 (13)

Title and authors Publication Year
Taking up the cudgels for the traditional reactive oxygen and nitrogen species detection assays and their use in the cardiovascular system
A Daiber, M Oelze, S Steven, S Kröller-Schön, T Münzel
Redox Biology 2017
Serelaxin Treatment Reduces Oxidative Stress and Increases Aldehyde Dehydrogenase-2 to Attenuate Nitrate Tolerance
CH Leo, DT Fernando, L Tran, HH Ng, SA Marshall, LJ Parry
Frontiers in pharmacology 2017
Argan Oil as an Effective Nutri-Therapeutic Agent in Metabolic Syndrome: A Preclinical Study
AE Midaoui, Y Haddad, Y Filali-Zegzouti, R Couture
International journal of molecular sciences 2017
Contemporary Approaches to Modulating the Nitric Oxide–cGMP Pathway in Cardiovascular Disease
JR Kraehling, WC Sessa
Circulation research 2017
Nitrite and Nitrate in Human Health and Disease
T Münzel, A Daiber
Nitrite and Nitrate in Human Health and Disease 2017
Taking up the cudgels for the traditional reactive oxygen and nitrogen species detection assays and their use in the cardiovascular system
A Daiber, M Oelze, S Steven, S Kröller-Schön, T Münzel
Redox Biology 2017
Analysis of the acute response of Galleria mellonella larvae to potassium nitrate
R Maguire, M Kunc, P Hyrsl, K Kavanagh
Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 2017
Kininase 1 As a Preclinical Therapeutic Target for Kinin B1 Receptor in Insulin Resistance
Y Haddad, R Couture
Frontiers in pharmacology 2017
Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids
MC Diniz, VC Olivon, LD Tavares, JA Simplicio, NA Gonzaga, DG de Souza, LM Bendhack, CR Tirapelli, D Bonaventura
Life Sciences 2017
The nitric oxide donor RuBPY does not induce in vitro cross-tolerance with acetylcholine
M Paulo, MD Grando, RS da Silva, RD Minshall, LM Bendhack
Nitric Oxide 2017
Localization and Interaction between Kinin B1 Receptor and NADPH Oxidase in the Vascular System of Diabetic Rats
Y Haddad, R Couture
Frontiers in physiology 2017
Angeli's Salt, a nitroxyl anion donor, reverses endothelin-1 mediated vascular dysfunction in murine aorta
BM Wynne, H Labazi, ZN Carneiro, RC Tostes, RC Webb
European Journal of Pharmacology 2017
Basic in vitro Characterization of the Vasodilatory Potential of 2-Aminoethyl Nitrate Fixed-Dose Combinations with Cilostazol, Metoprolol and Valsartan
M Oelze, P Welschof, M Knorr, LP Tran, E Ullmann, P Stamm, S Kröller-Schön, T Jansen, M Kopp, E Schulz, T Gori, K Burgin, A Scherhag, D Sartor, T Münzel, A Daiber
Pharmacology 2017

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 12 patents
Referenced in 3 Wikipedia pages
Referenced in 1 clinical guideline sources
48 readers on Mendeley
See more details