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Angiotensin II and Superoxide Generation

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Systems Biology of Free Radicals and Antioxidants

Abstract

Superoxide production plays an important role in the pathophysiological conditions mediated by angiotensin II. It has been shown that inhibition of AT1R inhibits cellular superoxide production and attenuates redox-dependent cell signaling. Animal and cell culture experiments showed that angiotensin II increases superoxide production by NADPH oxidases, uncoupled nitric oxide synthase, xanthine oxidase, and mitochondria. Meanwhile, specific molecular mechanisms of angiotensin II-mediated regulation of superoxide production are not completely understood. In this chapter, we review cellular sources of superoxide and their potential regulations by angiotensin II. Although angiotensin II directly stimulates NADPH oxidases, this results in redox-dependent activation of superoxide production by other cellular sources. It has become clear that cellular sources of superoxide represent a redox-sensitive network which constitutes a feedforward cycle. This mechanism amplifies redox signal under physiological conditions but may represent a vicious cycle of oxidative stress under pathological conditions leading to uncontrolled redox signaling events and cell and tissue dysfunction.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Sergey I. Dikalov & David G. Harrison

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  1. Sergey I. Dikalov
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  2. David G. Harrison
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Correspondence to Sergey I. Dikalov .

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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Dikalov, S.I., Harrison, D.G. (2014). Angiotensin II and Superoxide Generation. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_59

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