Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension

Tohru Fukai, Martin R. Siegfried, Masuko Fukai, Kathy K. Griendling, David G. Harrison

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107±3 to 152±9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg · kg-1 · d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by ~2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 μmol/L) and PD985059 (30 μmol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 μmol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalCirculation Research
Volume85
Issue number1
DOIs
StatePublished - Jul 9 1999
Externally publishedYes

Fingerprint

Angiotensin II
Superoxide Dismutase
Hypertension
Organoids
Losartan
Mitogen-Activated Protein Kinase 1
Blood Vessels
Blood Pressure
Messenger RNA
NADPH Oxidase
Mitogen-Activated Protein Kinase Kinases
RNA Stability
Pathologic Processes
Renin-Angiotensin System
Ribonucleases
Oxidants
Smooth Muscle Myocytes
Aorta
Norepinephrine
Oxidoreductases

Keywords

  • Angiotensin II
  • Hypertension
  • Norepinephrine
  • Superoxide
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. / Fukai, Tohru; Siegfried, Martin R.; Fukai, Masuko; Griendling, Kathy K.; Harrison, David G.

In: Circulation Research, Vol. 85, No. 1, 09.07.1999, p. 23-28.

Research output: Contribution to journalArticle

Fukai, Tohru ; Siegfried, Martin R. ; Fukai, Masuko ; Griendling, Kathy K. ; Harrison, David G. / Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. In: Circulation Research. 1999 ; Vol. 85, No. 1. pp. 23-28.
@article{6793cab23a8b4ff4839488408a31889d,
title = "Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension",
abstract = "Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107±3 to 152±9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg · kg-1 · d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by ~2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 μmol/L) and PD985059 (30 μmol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 μmol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.",
keywords = "Angiotensin II, Hypertension, Norepinephrine, Superoxide, Superoxide dismutase",
author = "Tohru Fukai and Siegfried, {Martin R.} and Masuko Fukai and Griendling, {Kathy K.} and Harrison, {David G.}",
year = "1999",
month = "7",
day = "9",
doi = "10.1161/01.RES.85.1.23",
language = "English (US)",
volume = "85",
pages = "23--28",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension

AU - Fukai, Tohru

AU - Siegfried, Martin R.

AU - Fukai, Masuko

AU - Griendling, Kathy K.

AU - Harrison, David G.

PY - 1999/7/9

Y1 - 1999/7/9

N2 - Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107±3 to 152±9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg · kg-1 · d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by ~2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 μmol/L) and PD985059 (30 μmol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 μmol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.

AB - Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107±3 to 152±9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg · kg-1 · d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by ~2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 μmol/L) and PD985059 (30 μmol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 μmol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.

KW - Angiotensin II

KW - Hypertension

KW - Norepinephrine

KW - Superoxide

KW - Superoxide dismutase

UR - http://www.scopus.com/inward/record.url?scp=0033538649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033538649&partnerID=8YFLogxK

U2 - 10.1161/01.RES.85.1.23

DO - 10.1161/01.RES.85.1.23

M3 - Article

C2 - 10400907

AN - SCOPUS:0033538649

VL - 85

SP - 23

EP - 28

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -