Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice

Karine Laude, Hua Cai, Brono Fink, Nyssa Hoch, David S. Weber, Louise McCann, Georg Kojda, Tohru Fukai, Harald H.H.W. Schmidt, Sergey Dikalov, Santhini Ramasamy, Graciela Gamez, Kathy K. Griendling, David G. Harrison

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Protein levels and polymorphisms of p22phox have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22phox expression would alter vascular ROS production and hemodynamics by targeting p22phox expression to smooth muscle in transgenic (Tg)p22smc. mice. Aortas of Tgp22smc mice had increased p22phox and Nox1 protein levels and produced more Superoxide and H2O2. Surprisingly, endothelium-dependent relaxation and blood pressure in Tgp22smc mice were normal. Aortas of Tgp22smc mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tgp22smc mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tgp22smc mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular Superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tgp22smc mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N G-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H2O2 production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Hemodynamics
Nitric Oxide
Superoxide Dismutase
Blood Vessels
Reactive Oxygen Species
Proteins
Nitric Oxide Synthase
Aorta
Calcium Ionophores
Nitric Oxide Synthase Type III
NADPH Oxidase
NG-Nitroarginine Methyl Ester
Electron Spin Resonance Spectroscopy
Glutathione Peroxidase
Superoxides
Catalase
Endothelium
Smooth Muscle
Oxidative Stress

Keywords

  • Endothelium
  • Nitric oxide
  • Oxidant stress
  • Transgenic animals

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice. / Laude, Karine; Cai, Hua; Fink, Brono; Hoch, Nyssa; Weber, David S.; McCann, Louise; Kojda, Georg; Fukai, Tohru; Schmidt, Harald H.H.W.; Dikalov, Sergey; Ramasamy, Santhini; Gamez, Graciela; Griendling, Kathy K.; Harrison, David G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 1 57-1, 01.01.2005.

Research output: Contribution to journalArticle

Laude, K, Cai, H, Fink, B, Hoch, N, Weber, DS, McCann, L, Kojda, G, Fukai, T, Schmidt, HHHW, Dikalov, S, Ramasamy, S, Gamez, G, Griendling, KK & Harrison, DG 2005, 'Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice', American Journal of Physiology - Heart and Circulatory Physiology, vol. 288, no. 1 57-1. https://doi.org/10.1152/ajpheart.00637.2004
Laude, Karine ; Cai, Hua ; Fink, Brono ; Hoch, Nyssa ; Weber, David S. ; McCann, Louise ; Kojda, Georg ; Fukai, Tohru ; Schmidt, Harald H.H.W. ; Dikalov, Sergey ; Ramasamy, Santhini ; Gamez, Graciela ; Griendling, Kathy K. ; Harrison, David G. / Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 1 57-1.
@article{97dfbd2599684063b8208d7c41adabd5,
title = "Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice",
abstract = "Protein levels and polymorphisms of p22phox have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22phox expression would alter vascular ROS production and hemodynamics by targeting p22phox expression to smooth muscle in transgenic (Tg)p22smc. mice. Aortas of Tgp22smc mice had increased p22phox and Nox1 protein levels and produced more Superoxide and H2O2. Surprisingly, endothelium-dependent relaxation and blood pressure in Tgp22smc mice were normal. Aortas of Tgp22smc mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tgp22smc mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tgp22smc mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular Superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tgp22smc mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N G-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H2O2 production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics.",
keywords = "Endothelium, Nitric oxide, Oxidant stress, Transgenic animals",
author = "Karine Laude and Hua Cai and Brono Fink and Nyssa Hoch and Weber, {David S.} and Louise McCann and Georg Kojda and Tohru Fukai and Schmidt, {Harald H.H.W.} and Sergey Dikalov and Santhini Ramasamy and Graciela Gamez and Griendling, {Kathy K.} and Harrison, {David G.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00637.2004",
language = "English (US)",
volume = "288",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 57-1",

}

TY - JOUR

T1 - Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice

AU - Laude, Karine

AU - Cai, Hua

AU - Fink, Brono

AU - Hoch, Nyssa

AU - Weber, David S.

AU - McCann, Louise

AU - Kojda, Georg

AU - Fukai, Tohru

AU - Schmidt, Harald H.H.W.

AU - Dikalov, Sergey

AU - Ramasamy, Santhini

AU - Gamez, Graciela

AU - Griendling, Kathy K.

AU - Harrison, David G.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Protein levels and polymorphisms of p22phox have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22phox expression would alter vascular ROS production and hemodynamics by targeting p22phox expression to smooth muscle in transgenic (Tg)p22smc. mice. Aortas of Tgp22smc mice had increased p22phox and Nox1 protein levels and produced more Superoxide and H2O2. Surprisingly, endothelium-dependent relaxation and blood pressure in Tgp22smc mice were normal. Aortas of Tgp22smc mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tgp22smc mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tgp22smc mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular Superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tgp22smc mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N G-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H2O2 production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics.

AB - Protein levels and polymorphisms of p22phox have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22phox expression would alter vascular ROS production and hemodynamics by targeting p22phox expression to smooth muscle in transgenic (Tg)p22smc. mice. Aortas of Tgp22smc mice had increased p22phox and Nox1 protein levels and produced more Superoxide and H2O2. Surprisingly, endothelium-dependent relaxation and blood pressure in Tgp22smc mice were normal. Aortas of Tgp22smc mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tgp22smc mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tgp22smc mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular Superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tgp22smc mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N G-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H2O2 production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics.

KW - Endothelium

KW - Nitric oxide

KW - Oxidant stress

KW - Transgenic animals

UR - http://www.scopus.com/inward/record.url?scp=19944403875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944403875&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00637.2004

DO - 10.1152/ajpheart.00637.2004

M3 - Article

VL - 288

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1 57-1

ER -