NYMC Faculty Publications
Antioxidants Condition Pleiotropic Vascular Responses to Exogenous H(2)O(2): Role of Modulation of Vascular TP Receptors and the Heme Oxygenase System
Author Type(s)
Faculty
DOI
10.1089/ars.2012.4587
Journal Title
Antioxidants & Redox Signaling
First Page
471
Last Page
480
Document Type
Article
Publication Date
2-10-2013
Department
Pharmacology
Keywords
15-Hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5, 13-dienoic Acid, Animals, Antioxidants, Base Sequence, Blood Vessels, Bridged Bicyclo Compounds, Heterocyclic, DNA Primers, Enzyme Inhibitors, Fatty Acids, Unsaturated, Heme Oxygenase (Decyclizing), Hydrazines, Hydrogen Peroxide, Imidazoles, Male, Pyridines, Rats, Rats, Sprague-Dawley, Receptors, Thromboxane
Disciplines
Medicine and Health Sciences
Abstract
AIMS: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.
RESULTS: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p
INNOVATIONS: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) did not increase vascular thromboxane B(2) release; instead, it sensitized the vasculature to a TP agonist, U46619, an effect reversed by PEG-SOD. Antioxidant-conditioned dilatory response to H(2)O(2) was accompanied by enhanced vascular heme oxygenase (HO)-dependent carbon monoxide generation and was abolished by HO inhibitors or by HO-1 & 2 antisense oligodeoxynucleotides treatment of SD rats.
CONCLUSION: These results demonstrate that H(2)O(2) has antioxidant-modifiable pleiotropic vascular effects, where constriction and dilation are brought about in the same vascular segment. H(2)O(2)-induced oxidative stress increases vascular TP sensitivity and predisposes these arterial segments to constrictor prostanoids. Conversely, vasodilation is reliant upon HO-derived products whose synthesis is stimulated only in the presence of antioxidants targeting radicals downstream of H(2)O(2).
Recommended Citation
Puri, N., Zhang, F. F., Monu, S. R., Sodhi, K., Bellner, L., Lamon, B. D., Zhang, Y., Abraham, N. G., & Nasjletti, A. (2013). Antioxidants Condition Pleiotropic Vascular Responses to Exogenous H(2)O(2): Role of Modulation of Vascular TP Receptors and the Heme Oxygenase System. Antioxidants & Redox Signaling, 18 (5), 471-480. https://doi.org/10.1089/ars.2012.4587
