Galina Yu. Mironova, Neil Mazumdar, Ahmed M. Hashad, Mohammed A. El-Lakany, Donald G. Welsh
{"title":"确定NADPH氧化酶在肌原性张力发育中的作用","authors":"Galina Yu. Mironova, Neil Mazumdar, Ahmed M. Hashad, Mohammed A. El-Lakany, Donald G. Welsh","doi":"10.1111/micc.12756","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>The myogenic response sets the foundation for blood flow control. Recent findings suggest a role for G protein-coupled receptors (GPCR) and signaling pathways tied to the generation of reactive oxygen species (ROS). In this regard, this study ascertained the impact of NADPH oxidase (Nox) on myogenic tone in rat cerebral resistance arteries.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The study employed real-time qPCR (RT-qPCR), pressure myography, and immunohistochemistry.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>G<sub>q</sub> blockade abolished myogenic tone in rat cerebral arteries, linking GPCR to mechanosensation. Subsequent work revealed that general (TEMPOL) and mitochondrial specific (MitoTEMPO) ROS scavengers had little impact on myogenic tone, whereas apocynin, a broad spectrum Nox inhibitor, initiated transient dilation. RT-qPCR revealed Nox1 and Nox2 mRNA expression in smooth muscle cells. Pressure myography defined Nox1 rather than Nox2 is facilitating myogenic tone. We rationalized that Nox1-generated ROS was initiating this response by impairing the ability of the Ca<sub>V</sub>3.2 channel to elicit negative feedback via BK<sub>Ca</sub>. This hypothesis was confirmed in functional experiments. The proximity ligation assay further revealed that Nox1 and Ca<sub>V</sub>3.2 colocalize within 40 nm of one another.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our data highlight that vascular pressurization augments Nox1 activity and ensuing ROS production facilitates myogenic tone by limiting Ca<sup>2+</sup> influx via Ca<sub>V</sub>3.2.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Defining a role of NADPH oxidase in myogenic tone development\",\"authors\":\"Galina Yu. Mironova, Neil Mazumdar, Ahmed M. Hashad, Mohammed A. El-Lakany, Donald G. Welsh\",\"doi\":\"10.1111/micc.12756\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>The myogenic response sets the foundation for blood flow control. Recent findings suggest a role for G protein-coupled receptors (GPCR) and signaling pathways tied to the generation of reactive oxygen species (ROS). In this regard, this study ascertained the impact of NADPH oxidase (Nox) on myogenic tone in rat cerebral resistance arteries.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The study employed real-time qPCR (RT-qPCR), pressure myography, and immunohistochemistry.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>G<sub>q</sub> blockade abolished myogenic tone in rat cerebral arteries, linking GPCR to mechanosensation. Subsequent work revealed that general (TEMPOL) and mitochondrial specific (MitoTEMPO) ROS scavengers had little impact on myogenic tone, whereas apocynin, a broad spectrum Nox inhibitor, initiated transient dilation. RT-qPCR revealed Nox1 and Nox2 mRNA expression in smooth muscle cells. Pressure myography defined Nox1 rather than Nox2 is facilitating myogenic tone. We rationalized that Nox1-generated ROS was initiating this response by impairing the ability of the Ca<sub>V</sub>3.2 channel to elicit negative feedback via BK<sub>Ca</sub>. This hypothesis was confirmed in functional experiments. 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Defining a role of NADPH oxidase in myogenic tone development
Objective
The myogenic response sets the foundation for blood flow control. Recent findings suggest a role for G protein-coupled receptors (GPCR) and signaling pathways tied to the generation of reactive oxygen species (ROS). In this regard, this study ascertained the impact of NADPH oxidase (Nox) on myogenic tone in rat cerebral resistance arteries.
Methods
The study employed real-time qPCR (RT-qPCR), pressure myography, and immunohistochemistry.
Results
Gq blockade abolished myogenic tone in rat cerebral arteries, linking GPCR to mechanosensation. Subsequent work revealed that general (TEMPOL) and mitochondrial specific (MitoTEMPO) ROS scavengers had little impact on myogenic tone, whereas apocynin, a broad spectrum Nox inhibitor, initiated transient dilation. RT-qPCR revealed Nox1 and Nox2 mRNA expression in smooth muscle cells. Pressure myography defined Nox1 rather than Nox2 is facilitating myogenic tone. We rationalized that Nox1-generated ROS was initiating this response by impairing the ability of the CaV3.2 channel to elicit negative feedback via BKCa. This hypothesis was confirmed in functional experiments. The proximity ligation assay further revealed that Nox1 and CaV3.2 colocalize within 40 nm of one another.
Conclusions
Our data highlight that vascular pressurization augments Nox1 activity and ensuing ROS production facilitates myogenic tone by limiting Ca2+ influx via CaV3.2.
期刊介绍：
The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation.
Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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