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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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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 2007 (24)

Title and authors Publication Year
Profiles in Cardiology
DG Harrison, JW Hurst
Clinical Cardiology 2007
Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in Humans
GR Thomas, JM DiFabio, T Gori, JD Parker
Journal of the American College of Cardiology 2007
Recent developments in nitric oxide donor drugs
MR Miller, IL Megson
British Journal of Pharmacology 2007
Oxidative Inhibition of the Mitochondrial Aldehyde Dehydrogenase Promotes Nitroglycerin Tolerance in Human Blood Vessels
U Hink, A Daiber, N Kayhan, J Trischler, C Kraatz, M Oelze, H Mollnau, P Wenzel, CF Vahl, KK Ho, H Weiner, T Munzel
Journal of the American College of Cardiology 2007
Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight
T Gori, GD Stolfo, S Sicuro, S Dragoni, M Lisi, S Forconi, JD Parker
British Journal of Clinical Pharmacology 2007
New insights into bioactivation of organic nitrates, nitrate tolerance and cross-tolerance
A Daiber, P Wenzel, M Oelze, T Münzel
Clinical Research in Cardiology 2007
Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2−/− mice
P Wenzel, U Hink, M Oelze, A Seeling, T Isse, K Bruns, L Steinhoff, M Brandt, AL Kleschyov, E Schulz, K Lange, H Weiner, J Lehmann, KJ Lackner, T Kawamoto, T Münzel, A Daiber
British Journal of Pharmacology 2007
Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation
K Szöcs, B Lassègue, P Wenzel, M Wendt, A Daiber, M Oelze, T Meinertz, T Münzel, S Baldus
Journal of Molecular and Cellular Cardiology 2007
Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation
N Sayed, P Baskaran, X Ma, F Akker, A Beuve
Proceedings of the National Academy of Sciences 2007
The kinin B1receptor antagonist SSR240612 reverses tactile and cold allodynia in an experimental rat model of insulin resistance
JP Dias, MA Ismael, M Pilon, J Champlain, B Ferrari, P Carayon, R Couture
British Journal of Pharmacology 2007
Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention
A Munteanu, JM Zingg
Molecular Aspects of Medicine 2007
Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats
T Ishizuka, A Niwa, M Tabuchi, Y Nagatani, K Ooshima, H Higashino
Journal of Hypertension 2007
Do We Still Need Organic Nitrates?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology
T Münzel, P Wenzel, A Daiber
Journal of the American College of Cardiology 2007
Evaluation of Pharmacological Modulation of Nitroglycerin-Induced Impairment of Nitric Oxide Bioavailability by a Catheter-Type Nitric Oxide Sensor
T Imanishi, A Kuroi, H Ikejima, S Mochizuki, M Goto, T Akasaka
Circulation Journal 2007
Nitratbehandlung
T Münzel, F Post
Clinical Research in Cardiology Supplements 2007
Risk of Mortality with Vitamin E Supplements: The Cache County Study
KM Hayden, KA Welsh-Bohmer, HJ Wengreen, PP Zandi, CG Lyketsos, JC Breitner
The American Journal of Medicine 2007
Chronic nitrates blunt the effects of not only nitric oxide but also natriuretic peptides in cardiac myocytes
T Tan, Q Zhang, C Anyadike, PM Scholz, HR Weiss
Pharmacological research : the official journal of the Italian Pharmacological Society 2007
Role of endogenous hydrogen peroxide in the development of nitrate tolerance
S Ghatta, RB Hemmer, S Uppala, ST O'Rourke
Vascular Pharmacology 2007
Ozonized autohemotransfusion does not affect arterial vasodilation in patients with peripheral arterial disease
A Coppola, L Coppola, C Luongo, A Arciello, F Cacciapuoti, D Lama, M Luongo, L Ruggiero, A Pastore, G Gombos
International Journal of Angiology 2007
Cardiovascular Therapeutics
MJ Landzberg
Cardiovascular Therapeutics 2007
Reduction in soluble guanylyl cyclase-specific activity following prolonged treatment of porcine pulmonary artery with nitric oxide
WJ Perkins, M Taniguchi, DO Warner, EN Chini, KA Jones
American journal of physiology. Lung cellular and molecular physiology 2007
Organic Nitrates and Tolerance in Cardiovascular Diseases: Effects of Isosorbide-2-Mononitrate Compared to Traditional Nitrates
R Raddino, G Caretta, D Robba, G Zanini, I Bonadei, A Madureri, LD Cas
Heart International 2007
Endothelial Dysfunction in Heart Failure and Ischemic Heart Disease: Rationale for the Clinical use of Mononitrates
O Parodi, RD Maria, E Roubina
Heart International 2007
In Vitro Tolerance of Mononitrates and Effects on Aggregation of Blood Platelets
E Lampa, A Filippelli
Heart International 2007

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