Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats
Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The presen...
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| Veröffentlicht in: | Neuroscience bulletin 2020-05, Vol.36 (5), p.475-492 |
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| creator | Hu, Li Zhang, Shutian Ooi, Kokwin Wu, Xuehai Wu, Jiaxiang Cai, Jian Sun, Yinggang Wang, Jijiang Zhu, Danian Chen, Fuxue Xia, Chunmei |
| description | Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension. |
| doi_str_mv | 10.1007/s12264-020-00484-9 |
| format | Article |
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Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.</description><identifier>ISSN: 1673-7067</identifier><identifier>EISSN: 1995-8218</identifier><identifier>DOI: 10.1007/s12264-020-00484-9</identifier><identifier>PMID: 32242284</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Anatomy ; Anesthesiology ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Blood Pressure - drug effects ; Heterocyclic Compounds, 4 or More Rings - pharmacology ; Human Physiology ; Hypertension ; Hypertension - metabolism ; Hypertension - physiopathology ; Male ; Medulla Oblongata - metabolism ; Microglia - metabolism ; Neurology ; Neurophysiology ; Neurosciences ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Original ; Original Article ; Pain Medicine ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface - metabolism ; Renin - metabolism ; Stress, Physiological ; Sulfones - pharmacology ; Sympathetic Nervous System - drug effects</subject><ispartof>Neuroscience bulletin, 2020-05, Vol.36 (5), p.475-492</ispartof><rights>The Author(s) 2020</rights><rights>COPYRIGHT 2020 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-937b1919996ec62badd27cfad9a7f247af68afb392bbf97bfa5ebc00abe6654e3</citedby><cites>FETCH-LOGICAL-c579t-937b1919996ec62badd27cfad9a7f247af68afb392bbf97bfa5ebc00abe6654e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186257/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186257/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32242284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Li</creatorcontrib><creatorcontrib>Zhang, Shutian</creatorcontrib><creatorcontrib>Ooi, Kokwin</creatorcontrib><creatorcontrib>Wu, Xuehai</creatorcontrib><creatorcontrib>Wu, Jiaxiang</creatorcontrib><creatorcontrib>Cai, Jian</creatorcontrib><creatorcontrib>Sun, Yinggang</creatorcontrib><creatorcontrib>Wang, Jijiang</creatorcontrib><creatorcontrib>Zhu, Danian</creatorcontrib><creatorcontrib>Chen, Fuxue</creatorcontrib><creatorcontrib>Xia, Chunmei</creatorcontrib><title>Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats</title><title>Neuroscience bulletin</title><addtitle>Neurosci. Bull</addtitle><addtitle>Neurosci Bull</addtitle><description>Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.</description><subject>Anatomy</subject><subject>Anesthesiology</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood Pressure - drug effects</subject><subject>Heterocyclic Compounds, 4 or More Rings - pharmacology</subject><subject>Human Physiology</subject><subject>Hypertension</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - physiopathology</subject><subject>Male</subject><subject>Medulla Oblongata - metabolism</subject><subject>Microglia - metabolism</subject><subject>Neurology</subject><subject>Neurophysiology</subject><subject>Neurosciences</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Original</subject><subject>Original Article</subject><subject>Pain Medicine</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Renin - metabolism</subject><subject>Stress, Physiological</subject><subject>Sulfones - pharmacology</subject><subject>Sympathetic Nervous System - drug effects</subject><issn>1673-7067</issn><issn>1995-8218</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9UV1rFDEUHUSxtfoHfJCAz6mZzGwyeRGWttrCVsv68RoymZttymyyJNmF_g7_sHccLRZEEkhy7znn3ptTVa9rdlozJt_lmnPRUsYZZaztWqqeVMe1Ugva8bp7inchGyqZkEfVi5zvGBNMNu3z6qjhvOW8a4-rH9feprgZvaHnkPwBBvJptb5pyNIWfzDFx0CuYfCmQCblFshNgpxjIhfOgS0kOozEBMEHgntCrGMuyYzkO4SS4ojM6YUi-3E0E-FLmTToVRj2Futd3u8gFQgZq5O1Kfll9cyZMcOr3-dJ9e3DxdezS7r6_PHqbLmidiFVoaqRfa1wXiXACt6bYeDSOjMoIx1vpXGiM65vFO97p2TvzAJ6y5jpQYhFC81J9X7W3e37LQx26teMepf81qR7HY3XjzPB3-pNPGhZd4IvJAq8nQU2ZgTtg4sIs1ufrV7KWiouBG8RdfoPFK4Btt7GAM5j_BGBzwR0JucE7qGlmunJeT07r9F5_ct5rZD05u9hHih_rEZAMwMypsIGkr6L-xTwg_8n-xPU-bz-</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Hu, Li</creator><creator>Zhang, Shutian</creator><creator>Ooi, Kokwin</creator><creator>Wu, Xuehai</creator><creator>Wu, Jiaxiang</creator><creator>Cai, Jian</creator><creator>Sun, Yinggang</creator><creator>Wang, Jijiang</creator><creator>Zhu, Danian</creator><creator>Chen, Fuxue</creator><creator>Xia, Chunmei</creator><general>Springer Singapore</general><general>Springer</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200501</creationdate><title>Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats</title><author>Hu, Li ; 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Bull</stitle><addtitle>Neurosci Bull</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>36</volume><issue>5</issue><spage>475</spage><epage>492</epage><pages>475-492</pages><issn>1673-7067</issn><eissn>1995-8218</eissn><abstract>Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>32242284</pmid><doi>10.1007/s12264-020-00484-9</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anatomy Anesthesiology Animals Biomedical and Life Sciences Biomedicine Blood Pressure - drug effects Heterocyclic Compounds, 4 or More Rings - pharmacology Human Physiology Hypertension Hypertension - metabolism Hypertension - physiopathology Male Medulla Oblongata - metabolism Microglia - metabolism Neurology Neurophysiology Neurosciences NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Original Original Article Pain Medicine Rats Rats, Sprague-Dawley Receptors, Cell Surface - metabolism Renin - metabolism Stress, Physiological Sulfones - pharmacology Sympathetic Nervous System - drug effects |
| title | Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats |
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