Research ExplorerPublicationsIncreased superoxide production in nitrate tolerance is asso...

Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation

Standard

Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation. / Szöcs, Katalin; Lassègue, Bernard; Wenzel, Philip; Wendt, Maria; Daiber, Andreas; Oelze, Matthias; Meinertz, Thomas; Münzel, Thomas; Baldus, Stephan.

In: J MOL CELL CARDIOL, Vol. 42, No. 6, 06.2007, p. 1111-1118.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Szöcs, K, Lassègue, B, Wenzel, P, Wendt, M, Daiber, A, Oelze, M, Meinertz, T, Münzel, T & Baldus, S 2007, 'Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation', J MOL CELL CARDIOL, vol. 42, no. 6, pp. 1111-1118. https://doi.org/10.1016/j.yjmcc.2007.03.904

APA

Szöcs, K., Lassègue, B., Wenzel, P., Wendt, M., Daiber, A., Oelze, M., Meinertz, T., Münzel, T., & Baldus, S. (2007). Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation. J MOL CELL CARDIOL, 42(6), 1111-1118. https://doi.org/10.1016/j.yjmcc.2007.03.904

Vancouver

Szöcs K, Lassègue B, Wenzel P, Wendt M, Daiber A, Oelze M et al. Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation. J MOL CELL CARDIOL. 2007 Jun;42(6):1111-1118. https://doi.org/10.1016/j.yjmcc.2007.03.904

Bibtex

@article{e2e4ec173276433aa81214c4ab3a0de0,
title = "Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation",
abstract = "Chronic administration of nitroglycerin (NTG) induces nitrate tolerance. Among possible underlying mechanisms, increased vascular production of reactive oxygen species (ROS) has emerged as a principal mechanism. Using cell culture and animal models of nitrate tolerance, we aimed to assess the impact of nitrates on NAD(P)H oxidases and aldehyde dehydrogenase 2 (ALDH2) expression. Rats and vascular smooth muscle cells were treated with NTG. Vascular reactivity was assessed by isometric tension studies. Superoxide was detected by dihydroethidium staining. Gene expression was measured by real-time polymerase chain reaction. NAD(P)H oxidase activity was measured using lucigenin-enhanced chemiluminescence. ALDH activity was measured biochemically, and NO consumption electrochemically. Nitrate tolerance was induced in rats by treatment with NTG for 3 days, and detected as impaired endothelium-dependent and -independent relaxation of aortic segments. Although superoxide production was increased in all aortic layers, expression of nox1, nox2 and nox4 was significantly decreased. Similarly, in vascular smooth muscle cells exposed to NTG for 6-24 h, NAD(P)H oxidase activity was increased, in spite of nox1 downregulation. In addition, expression and activity of ALDH-2 was decreased in nitrate-tolerant rings. Furthermore, exogenous addition of ALDH decreased superoxide generation in vitro and attenuated NO consumption in vascular smooth muscle cell homogenates. Our data suggest that in nitrate tolerance, activation of nox enzymes more than compensates for their downregulation, resulting in a net increase in superoxide and NO consumption. Furthermore, reduced ALDH-2 activity and expression leads to decreased NTG bioconversion. Therefore, both mechanisms reduce NO availability and impair vasorelaxation.",
keywords = "Aldehyde Dehydrogenase/genetics, Animals, Drug Tolerance, Gene Expression Regulation, Enzymologic/drug effects, Male, NADPH Oxidases/genetics, Nitroglycerin/pharmacology, Rats, Rats, Wistar, Superoxides/metabolism, Vasodilator Agents/pharmacology",
author = "Katalin Sz{\"o}cs and Bernard Lass{\`e}gue and Philip Wenzel and Maria Wendt and Andreas Daiber and Matthias Oelze and Thomas Meinertz and Thomas M{\"u}nzel and Stephan Baldus",
year = "2007",
month = jun,
doi = "10.1016/j.yjmcc.2007.03.904",
language = "English",
volume = "42",
pages = "1111--1118",
journal = "J MOL CELL CARDIOL",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - Increased superoxide production in nitrate tolerance is associated with NAD(P)H oxidase and aldehyde dehydrogenase 2 downregulation

AU - Szöcs, Katalin

AU - Lassègue, Bernard

AU - Wenzel, Philip

AU - Wendt, Maria

AU - Daiber, Andreas

AU - Oelze, Matthias

AU - Meinertz, Thomas

AU - Münzel, Thomas

AU - Baldus, Stephan

PY - 2007/6

Y1 - 2007/6

N2 - Chronic administration of nitroglycerin (NTG) induces nitrate tolerance. Among possible underlying mechanisms, increased vascular production of reactive oxygen species (ROS) has emerged as a principal mechanism. Using cell culture and animal models of nitrate tolerance, we aimed to assess the impact of nitrates on NAD(P)H oxidases and aldehyde dehydrogenase 2 (ALDH2) expression. Rats and vascular smooth muscle cells were treated with NTG. Vascular reactivity was assessed by isometric tension studies. Superoxide was detected by dihydroethidium staining. Gene expression was measured by real-time polymerase chain reaction. NAD(P)H oxidase activity was measured using lucigenin-enhanced chemiluminescence. ALDH activity was measured biochemically, and NO consumption electrochemically. Nitrate tolerance was induced in rats by treatment with NTG for 3 days, and detected as impaired endothelium-dependent and -independent relaxation of aortic segments. Although superoxide production was increased in all aortic layers, expression of nox1, nox2 and nox4 was significantly decreased. Similarly, in vascular smooth muscle cells exposed to NTG for 6-24 h, NAD(P)H oxidase activity was increased, in spite of nox1 downregulation. In addition, expression and activity of ALDH-2 was decreased in nitrate-tolerant rings. Furthermore, exogenous addition of ALDH decreased superoxide generation in vitro and attenuated NO consumption in vascular smooth muscle cell homogenates. Our data suggest that in nitrate tolerance, activation of nox enzymes more than compensates for their downregulation, resulting in a net increase in superoxide and NO consumption. Furthermore, reduced ALDH-2 activity and expression leads to decreased NTG bioconversion. Therefore, both mechanisms reduce NO availability and impair vasorelaxation.

AB - Chronic administration of nitroglycerin (NTG) induces nitrate tolerance. Among possible underlying mechanisms, increased vascular production of reactive oxygen species (ROS) has emerged as a principal mechanism. Using cell culture and animal models of nitrate tolerance, we aimed to assess the impact of nitrates on NAD(P)H oxidases and aldehyde dehydrogenase 2 (ALDH2) expression. Rats and vascular smooth muscle cells were treated with NTG. Vascular reactivity was assessed by isometric tension studies. Superoxide was detected by dihydroethidium staining. Gene expression was measured by real-time polymerase chain reaction. NAD(P)H oxidase activity was measured using lucigenin-enhanced chemiluminescence. ALDH activity was measured biochemically, and NO consumption electrochemically. Nitrate tolerance was induced in rats by treatment with NTG for 3 days, and detected as impaired endothelium-dependent and -independent relaxation of aortic segments. Although superoxide production was increased in all aortic layers, expression of nox1, nox2 and nox4 was significantly decreased. Similarly, in vascular smooth muscle cells exposed to NTG for 6-24 h, NAD(P)H oxidase activity was increased, in spite of nox1 downregulation. In addition, expression and activity of ALDH-2 was decreased in nitrate-tolerant rings. Furthermore, exogenous addition of ALDH decreased superoxide generation in vitro and attenuated NO consumption in vascular smooth muscle cell homogenates. Our data suggest that in nitrate tolerance, activation of nox enzymes more than compensates for their downregulation, resulting in a net increase in superoxide and NO consumption. Furthermore, reduced ALDH-2 activity and expression leads to decreased NTG bioconversion. Therefore, both mechanisms reduce NO availability and impair vasorelaxation.

KW - Aldehyde Dehydrogenase/genetics

KW - Animals

KW - Drug Tolerance

KW - Gene Expression Regulation, Enzymologic/drug effects

KW - Male

KW - NADPH Oxidases/genetics

KW - Nitroglycerin/pharmacology

KW - Rats

KW - Rats, Wistar

KW - Superoxides/metabolism

KW - Vasodilator Agents/pharmacology

U2 - 10.1016/j.yjmcc.2007.03.904

DO - 10.1016/j.yjmcc.2007.03.904

M3 - SCORING: Journal article

C2 - 17493633

VL - 42

SP - 1111

EP - 1118

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

IS - 6

ER -