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We previously reported that \u03b2\u2010arrestin\u20101, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)\u201022\u20103p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR\u201022\u20103p in \u03b2\u2010arrestin\u20101\u2010mediated central cardiovascular regulation in hypertension. It was observed that miR\u201022\u20103p was upregulated in the RVLM of SHRs compared with normotensive Wistar\u2013Kyoto (WKY) rats, and it was subsequently confirmed to target the \u03b2\u2010arrestin\u20101 gene using a dual\u2010luciferase reporter assay. miR\u201022\u20103p was downregulated in the RVLM using adeno\u2010associated virus with \u2018tough decoys\u2019, which caused a significant increase of \u03b2\u2010arrestin\u20101 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR\u201022\u20103p using lentivirus in the RVLM of WKY rats significantly increased BP. In <jats:italic>in vitro<\/jats:italic> PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR\u201022\u20103p inhibitor, and this effect could be abolished by \u03b2\u2010arrestin\u20101 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR\u201022\u20103p expression, and enhanced \u03b2\u2010arrestin\u20101 expression in the RVLM of SHRs. Activation of BV2 cells <jats:italic>in vitro<\/jats:italic> evoked a significant increase of miR\u201022\u20103p expression, and this BV2 cell culture medium was also able to facilitate miR\u201022\u20103p expression in PC12 cells. Collectively, our findings support a critical role for microglia\u2010derived miR\u201022\u20103p in inhibiting \u03b2\u2010arrestin\u20101 in the RVLM, which is involved in central cardiovascular regulation in hypertension.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15876-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Impairment of \u03b2\u2010arrestin\u20101 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of \u03b2\u2010arrestin\u20101 dysfunction in hypertension.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>miR\u201022\u20103p is implicated in multiple biological processes, but the role of miR\u201022\u20103p in central regulation of cardiovascular activity in hypertension remains unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We predicted that miR\u201022\u20103p could directly bind to the \u03b2\u2010arrestin\u20101 gene (<jats:italic>Arrb1<\/jats:italic>), and this hypothesis was confirmed by using a dual\u2010luciferase reporter assay. Inhibition of \u03b2\u2010arrestin\u20101 by miR\u201022\u20103p was further verified in both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Furthermore, our results suggested miR\u201022\u20103p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho\u2010excitation and hypertension.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our present study provides evidence that microglia\u2010derived miR\u201022\u20103p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting \u03b2\u2010arrestin\u20101 in the RVLM.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283960","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T08:28:15Z","timestamp":1703752095000},"page":"317-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["miR\u201022\u20103p in the rostral ventrolateral medulla promotes hypertension through inhibiting \u03b2\u2010arrestin\u20101"],"prefix":"10.1113","volume":"602","author":[{"given":"Wen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Marine Biomedicine and Polar Medicine, Naval Medical Center Naval Medical University (Second Military Medical University)  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-1531","authenticated-orcid":false,"given":"Jia\u2010Cen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Marine 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