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Review ArticleReview Article

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

Christopher S. Wilcox and Adam Pearlman
Pharmacological Reviews December 2008, 60 (4) 418-469; DOI: https://doi.org/10.1124/pr.108.000240
Christopher S. Wilcox
Division of Nephrology and Hypertension and Hypertension, Kidney and Vascular Disorder Center, Georgetown University, Washington DC
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Adam Pearlman
Division of Nephrology and Hypertension and Hypertension, Kidney and Vascular Disorder Center, Georgetown University, Washington DC
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Abstract

Nitroxides can undergo one- or two-electron reduction reactions to hydroxylamines or oxammonium cations, respectively, which themselves are interconvertible, thereby providing redox metabolic actions. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) is the most extensively studied nitroxide. It is a cell membrane-permeable amphilite that dismutates superoxide catalytically, facilitates hydrogen peroxide metabolism by catalase-like actions, and limits formation of toxic hydroxyl radicals produced by Fenton reactions. It is broadly effective in detoxifying these reactive oxygen species in cell and animal studies. When administered intravenously to hypertensive rodent models, tempol caused rapid and reversible dose-dependent reductions in blood pressure in 22 of 26 studies. This was accompanied by vasodilation, increased nitric oxide activity, reduced sympathetic nervous system activity at central and peripheral sites, and enhanced potassium channel conductance in blood vessels and neurons. When administered orally or by infusion over days or weeks to hypertensive rodent models, it reduced blood pressure in 59 of 68 studies. This was accompanied by correction of salt sensitivity and endothelial dysfunction and reduced agonist-evoked oxidative stress and contractility of blood vessels, reduced renal vascular resistance, and increased renal tissue oxygen tension. Thus, tempol is broadly effective in reducing blood pressure, whether given by acute intravenous injection or by prolonged administration, in a wide range of rodent models of hypertension.

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Pharmacological Reviews: 60 (4)
Pharmacological Reviews
Vol. 60, Issue 4
1 Dec 2008
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Review ArticleReview Article

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

Christopher S. Wilcox and Adam Pearlman
Pharmacological Reviews December 1, 2008, 60 (4) 418-469; DOI: https://doi.org/10.1124/pr.108.000240

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Review ArticleReview Article

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

Christopher S. Wilcox and Adam Pearlman
Pharmacological Reviews December 1, 2008, 60 (4) 418-469; DOI: https://doi.org/10.1124/pr.108.000240
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  • Article
    • Abstract
    • I. Introduction
    • II. Mechanistic Basis of the Blood Pressure-Lowering Effect of Tempol
    • III. Toxicity of Tempol
    • IV. Conclusions Concerning Blood Pressure-Lowering Actions of Tempol
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