Role of extracellular superoxide dismutase in hypertension

Maria Carolina Gongora, Zhenyu Qin, Karine Laude, Ha Won Kim, Louise McCann, J. Rodney Folz, Sergey Dikalov, Tohru Fukai, David G. Harrison

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalHypertension
Volume48
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Superoxide Dismutase
Hypertension
Angiotensin II
Vasodilation
Superoxides
Endothelium
Arterioles
NADP
Blood Vessels
Aorta
Copper
Oxidoreductases
Mesenteric Arteries
Nitric Oxide Synthase
Up-Regulation
Blood Pressure

Keywords

  • Angiotensin II
  • Endothelium
  • Hypertension, experimental
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Gongora, M. C., Qin, Z., Laude, K., Kim, H. W., McCann, L., Folz, J. R., ... Harrison, D. G. (2006). Role of extracellular superoxide dismutase in hypertension. Hypertension, 48(3), 473-481. https://doi.org/10.1161/01.HYP.0000235682.47673.ab

Role of extracellular superoxide dismutase in hypertension. / Gongora, Maria Carolina; Qin, Zhenyu; Laude, Karine; Kim, Ha Won; McCann, Louise; Folz, J. Rodney; Dikalov, Sergey; Fukai, Tohru; Harrison, David G.

In: Hypertension, Vol. 48, No. 3, 01.09.2006, p. 473-481.

Research output: Contribution to journalArticle

Gongora, MC, Qin, Z, Laude, K, Kim, HW, McCann, L, Folz, JR, Dikalov, S, Fukai, T & Harrison, DG 2006, 'Role of extracellular superoxide dismutase in hypertension', Hypertension, vol. 48, no. 3, pp. 473-481. https://doi.org/10.1161/01.HYP.0000235682.47673.ab
Gongora, Maria Carolina ; Qin, Zhenyu ; Laude, Karine ; Kim, Ha Won ; McCann, Louise ; Folz, J. Rodney ; Dikalov, Sergey ; Fukai, Tohru ; Harrison, David G. / Role of extracellular superoxide dismutase in hypertension. In: Hypertension. 2006 ; Vol. 48, No. 3. pp. 473-481.
@article{4117b27744434ad4ab6c44ec69ccbb97,
title = "Role of extracellular superoxide dismutase in hypertension",
abstract = "We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD mice, the activity of Cu/ZnSOD was increased by 80{\%} after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.",
keywords = "Angiotensin II, Endothelium, Hypertension, experimental, Nitric oxide",
author = "Gongora, {Maria Carolina} and Zhenyu Qin and Karine Laude and Kim, {Ha Won} and Louise McCann and Folz, {J. Rodney} and Sergey Dikalov and Tohru Fukai and Harrison, {David G.}",
year = "2006",
month = "9",
day = "1",
doi = "10.1161/01.HYP.0000235682.47673.ab",
language = "English (US)",
volume = "48",
pages = "473--481",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Role of extracellular superoxide dismutase in hypertension

AU - Gongora, Maria Carolina

AU - Qin, Zhenyu

AU - Laude, Karine

AU - Kim, Ha Won

AU - McCann, Louise

AU - Folz, J. Rodney

AU - Dikalov, Sergey

AU - Fukai, Tohru

AU - Harrison, David G.

PY - 2006/9/1

Y1 - 2006/9/1

N2 - We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.

AB - We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.

KW - Angiotensin II

KW - Endothelium

KW - Hypertension, experimental

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=33747404190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747404190&partnerID=8YFLogxK

U2 - 10.1161/01.HYP.0000235682.47673.ab

DO - 10.1161/01.HYP.0000235682.47673.ab

M3 - Article

VL - 48

SP - 473

EP - 481

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 3

ER -