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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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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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Citations to this article in year 2008 (19)

Title and authors Publication Year
The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles
B Mayer, M Beretta
British Journal of Pharmacology 2008
Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction
P Wenzel, S Schuhmacher, J Kienhofer, J Muller, M Hortmann, M Oelze, E Schulz, N Treiber, T Kawamoto, K Scharffetter-Kochanek, T Munzel, A Burkle, MM Bachschmid, A Daiber
Cardiovascular Research 2008
Nitric oxide-induced headache may arise from extracerebral arteries as judged from tolerance to isosorbide-5-mononitrate
I Christiansen, HK Iversen, J Olesen, P Tfelt-Hansen
The Journal of Headache and Pain 2008
First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction
P Wenzel, H Mollnau, M Oelze, E Schulz, JM Wickramanayake, J Müller, S Schuhmacher, M Hortmann, S Baldus, T Gori, RP Brandes, T Münzel, A Daiber
Antioxidants & Redox Signaling 2008
Role of cGMP-dependent protein kinase in development of tolerance to nitroglycerine in porcine coronary arteries
D Dou, X Zheng, X Qin, H Qi, L Liu, JU Raj, Y Gao
British Journal of Pharmacology 2008
Nitroglycerin-Induced S-nitrosylation and Desensitization of Soluble Guanylyl Cyclase Contribute to Nitrate Tolerance
N Sayed, DD Kim, X Fioramonti, T Iwahashi, WN Duran, A Beuve
Circulation research 2008
Fundamental and Clinical Cardiology Series
PD Stein
Cardiovascular Disease in the Elderly 2008
Effects of chronicin vivoadministration of nitroglycerine on ACh-induced endothelium-dependent relaxation in rabbit cerebral arteries
Y Watanabe, N Kusama, T Itoh
British Journal of Pharmacology 2008
Comparative effects of <i>N</i>-acetyl-<span class="smallcap">l</span>-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats
AE Midaoui, MA Ismael, H Lu, IG Fantus, J Champlain, R Couture
Canadian Journal of Physiology and Pharmacology 2008
Antioxidative effects of statins
O Adam, U Laufs
Archives of Toxicology 2008
SUPPRESSING NADPH OXIDASE-DEPENDENT OXIDATIVE STRESS IN THE VASCULATURE WITH NITRIC OXIDE DONORS
S Selemidis
Clinical and Experimental Pharmacology and Physiology 2008
Cardiovascular disease in dialysis patients: do some antihypertensive drugs have specific antioxidant effects or is it just blood pressure reduction? Does antioxidant treatment reduce the risk for cardiovascular disease?
S Aslam
Current Opinion in Nephrology and Hypertension 2008
AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats
P Wenzel, E Schulz, M Oelze, J Müller, S Schuhmacher, MS Alhamdani, J Debrezion, M Hortmann, K Reifenberg, I Fleming, T Münzel, A Daiber
Free radical biology & medicine 2008
Secoisolariciresinol diglucoside induces neovascularization-mediated cardioprotection against ischemia-reperfusion injury in hypercholesterolemic myocardium
SV Penumathsa, S Koneru, L Zhan, S John, VP Menon, K Prasad, N Maulik
Journal of Molecular and Cellular Cardiology 2008
Dissociation between superoxide accumulation and nitroglycerin-induced tolerance
PS Tsou, V Addanki, HL Fung
The Journal of pharmacology and experimental therapeutics 2008
Sirolimus-induced vascular dysfunction. Increased mitochondrial and nicotinamide adenosine dinucleotide phosphate oxidase-dependent superoxide production and decreased vascular nitric oxide formation
A Jabs, S Göbel, P Wenzel, AL Kleschyov, M Hortmann, M Oelze, A Daiber, T Münzel
Journal of the American College of Cardiology 2008
Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats
T Ishizuka, A Niwa, M Tabuchi, K Ooshima, H Higashino
Life Sciences 2008
The role of lipoic acid in prevention of nitroglycerin tolerance
M Dudek, M Bednarski, A Bilska, M Iciek, M Sokołowska-Jeżewicz, B Filipek, L Włodek
European Journal of Pharmacology 2008
Soluble guanylyl cyclase activation by HMR-1766 (ataciguat) in cells exposed to oxidative stress
Z Zhou, A Pyriochou, A Kotanidou, G Dalkas, M Eickels, G Spyroulias, C Roussos, A Papapetropoulos
American journal of physiology. Heart and circulatory physiology 2008

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