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Cited by 223Nitric Oxide and Endothelin EffectsEicosanoids and Hypertension PharmacologyGlutathione Transferases and Polymorphisms

Extracellular Superoxide Dismutase Is a Major Determinant of Nitric Oxide Bioavailability: In Vivo and Ex Vivo Evidence From ecSOD-Deficient Mice

Jung, Oliver, Marklund, Stefan L., Geiger, Helmut, Pedrazzini, Thierry, Busse, Rudi, Brandes, Ralf P.·2003·Circulation Research
DOI 10.1161/01.res.0000092140.81594.a8
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Abstract

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O 2 ·− ). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O 2 ·− is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II–induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD +/+ and ecSOD −/− mice. After 6 days of angiotensin II–treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD −/− than ecSOD +/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD −/− mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD +/+ mice. Compared with sham-operated ecSOD +/+ mice, sham-operated ecSOD −/− mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O 2 ·− , as measured by lucigenin chemiluminescence, was higher in ecSOD −/− compared with ecSOD +/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD −/− , as well as from clipped ecSOD +/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD −/− mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O 2 ·− , controlling blood pressure and vascular function in angiotensin II–dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.

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  • Endothelial dysfunction, characterized by a lack of dilation of blood vessels in response to endothelium-dependent vasoactive substances such as acetylcholine, is consistent with a deficiency of bioavailable nitric oxide.

    “Endothelial dysfunction, characterized by a lack of dilation of blood vessels in response to endothelium-dependent vasoactive substances, such as acetylcholine, is consistent with a deficiency of bioavailable NO· (158, 200, 266).”

    From Redox regulation of mitochondrial function (2012) · cites this paper as [200]

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Authors
Jung, O., Marklund, S. L., Geiger, H., Pedrazzini, T., Busse, R., & Brandes, R. P.
Affiliations
Goethe University Frankfurt (DE)
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2003-10-03
Volume
93
Issue
7
Pages
622-629
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/01.res.0000092140.81594.a8
OpenAlex
W2137861969
Cited by
223
References
31
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 15 · 2012: 19
FWCI
9.39
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
extracellular superoxide dismutase, nitric oxide bioavailability, superoxide, angiotensin II-induced hypertension, renovascular hypertension, two-kidney one-clip model, blood pressure regulation, endothelium-dependent relaxation, acetylcholine-induced vasodilation, oxidative stress, lucigenin chemiluminescence, vascular function
MeSH terms
Acetylcholine, Angiotensin II, Animals, Blood Pressure, Catalase, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Humans, Hypertension, Hypertension, Renovascular, Male, Nitric Oxide, Nitroprusside, Phenylephrine, Recombinant Proteins, Superoxides, Superoxide Dismutase, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents, Blotting, Western, Mice, Knockout, Mice, In Vitro Techniques

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