© 1999 American Heart Association, Inc.
Original Contribution |
Modulation of Extracellular Superoxide Dismutase Expression by Angiotensin II and Hypertension
From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, and Atlanta Veterans Administration Hospital, Atlanta, Ga.
Correspondence to David G. Harrison, MD, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, WMB 319, Atlanta, GA 30322. E-mail dharr02{at}emory.edu
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.
Key Words: hypertension • angiotensin II • norepinephrine • superoxide • superoxide dismutase
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|
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