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Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction

BACKGROUND: Reactive oxygen species (ROS) were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α(1)-adrenoceptor-activated contraction by altering...

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Autores principales: Tsai, Ming-Ho, Jiang, Meei Jyh
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931462/
https://www.ncbi.nlm.nih.gov/pubmed/20727219
http://dx.doi.org/10.1186/1423-0127-17-67
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author Tsai, Ming-Ho
Jiang, Meei Jyh
author_facet Tsai, Ming-Ho
Jiang, Meei Jyh
author_sort Tsai, Ming-Ho
collection PubMed
description BACKGROUND: Reactive oxygen species (ROS) were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α(1)-adrenoceptor-activated contraction by altering myosin phosphatase activities. METHODS: Using endothelium-denuded rat tail artery (RTA) strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC(20)), and myosin phosphatase stimulated by α(1)-adrenoceptor agonist phenylephrine were examined. RESULTS: An antioxidant, N-acetyl-L-cysteine (NAC), and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC(20 )phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1(Thr855 )and myosin phosphatase inhibitor CPI-17(Thr38). CONCLUSIONS: ROS, probably derived from NADPH oxidase and mitochondria, partially regulate α(1)-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC(20 )phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways.
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spelling pubmed-29314622010-09-02 Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction Tsai, Ming-Ho Jiang, Meei Jyh J Biomed Sci Research BACKGROUND: Reactive oxygen species (ROS) were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α(1)-adrenoceptor-activated contraction by altering myosin phosphatase activities. METHODS: Using endothelium-denuded rat tail artery (RTA) strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC(20)), and myosin phosphatase stimulated by α(1)-adrenoceptor agonist phenylephrine were examined. RESULTS: An antioxidant, N-acetyl-L-cysteine (NAC), and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC(20 )phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1(Thr855 )and myosin phosphatase inhibitor CPI-17(Thr38). CONCLUSIONS: ROS, probably derived from NADPH oxidase and mitochondria, partially regulate α(1)-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC(20 )phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways. BioMed Central 2010-08-23 /pmc/articles/PMC2931462/ /pubmed/20727219 http://dx.doi.org/10.1186/1423-0127-17-67 Text en Copyright ©2010 Tsai and Jiang; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Tsai, Ming-Ho
Jiang, Meei Jyh
Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title_full Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title_fullStr Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title_full_unstemmed Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title_short Reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
title_sort reactive oxygen species are involved in regulating α(1)-adrenoceptor-activated vascular smooth muscle contraction
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931462/
https://www.ncbi.nlm.nih.gov/pubmed/20727219
http://dx.doi.org/10.1186/1423-0127-17-67
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