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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.
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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.

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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

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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
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Citations to this article in year 2009 (34)

Title and authors Publication Year
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Pharmacological induction of vascular extracellular superoxide dismutase expressionin vivo
M Oppermann, V Balz, V Adams, VT Dao, M Bas, T Suvorava, G Kojda
Journal of Cellular and Molecular Medicine 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
cGMP: Generators, Effectors and Therapeutic Implications
HH Schmidt, F Hofmann, JP Stasch
Handbook of experimental pharmacology 2009
A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena
S Schuhmacher, E Schulz, M Oelze, A König, C Roegler, K Lange, L Sydow, T Kawamoto, P Wenzel, T Münzel, J Lehmann, A Daiber
British Journal of Pharmacology 2009
Monitoring white blood cell mitochondrial aldehyde dehydrogenase activity: implications for nitrate therapy in humans
P Wenzel, E Schulz, T Gori, MA Ostad, F Mäthner, S Schildknecht, S Göbel, M Oelze, D Stalleicken, A Warnholtz, T Münzel, A Daiber
The Journal of pharmacology and experimental therapeutics 2009
Advanced Protocols in Oxidative Stress II
D Armstrong
2009
Advanced Protocols in Oxidative Stress II
D Armstrong
2009
Effect of Chronic Inhibition of Nitric Oxide on Hypertension, Insulin Resistance, and Cardiovascular Remodeling in Glucose-fed Rats
M Pilon, R Wu, JÉ Huot-Marchand, D deBlois, J Champlain, R Couture
Journal of Cardiovascular Pharmacology 2009
Understanding organic nitrates - a vein hope?
MR Miller, RM Wadsworth
British Journal of Pharmacology 2009
Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance
D Dou, H Ma, X Zheng, L Ying, Y Guo, X Yu, Y Gao
Cardiovascular Research 2009
Nitroglycerin Headache and Nitroglycerin-Induced Primary Headaches From 1846 and Onwards: A Historical Overview and an Update
PC Tfelt-Hansen, J Tfelt-Hansen
Headache: The Journal of Head and Face Pain 2009
Continuous therapy with transdermal nitroglycerin does not affect biomarkers of vascular inflammation and injury in healthy volunteers
GR Thomas, JM DiFabio, T Gori, DJ Jenkins, JD Parker
Canadian Journal of Physiology and Pharmacology 2009
Mitochondrial aldehyde dehydrogenase (ALDH-2)—Maker of and marker for nitrate tolerance in response to nitroglycerin treatment
A Daiber, P Wenzel, M Oelze, S Schuhmacher, T Jansen, T Münzel
Chemico-Biological Interactions 2009
Non-Hemodynamic Effects of Organic Nitrates and the Distinctive Characteristics of Pentaerithrityl Tetranitrate
T Gori, A Daiber
American Journal Cardiovascular Drugs 2009
Statins for post resuscitation syndrome
A Kämäräinen, I Virkkunen, T Silfvast, J Tenhunen
Medical Hypotheses 2009
Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress
A Daiber, M Oelze, P Wenzel, JM Wickramanayake, S Schuhmacher, T Jansen, KJ Lackner, M Torzewski, T Münzel
Pharmacological Reports 2009
New biomaterials for the sustained release of nitric oxide: past, present and future
A Friedman, J Friedman
Expert Opinion on Drug Delivery 2009
Effects of nitroglycerin or pentaerithrityl tetranitrate treatment on the gene expression in rat hearts: evidence for cardiotoxic and cardioprotective effects
A Pautz, P Rauschkolb, N Schmidt, J Art, M Oelze, P Wenzel, U Förstermann, A Daiber, H Kleinert
Physiological genomics 2009
Role of Glutaredoxin-Mediated Protein S -Glutathionylation in Cellular Nitroglycerin Tolerance
PS Tsou, V Addanki, JA Haas, NA Page, HL Fung
The Journal of pharmacology and experimental therapeutics 2009

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