{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:43:10Z","timestamp":1777725790613,"version":"3.51.4"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Baroreflex dysfunction is partly implicated in hypertension and one responsible region is the dorsal medulla oblongata including the nucleus tractus solitarius (NTS). NTS neurons receive and project glutamatergic inputs to subsequently regulate blood pressure, while G-protein-coupled metabotropic glutamate receptors (mGluRs) play a modulatory role for glutamatergic transmission in baroreflex pathways. Stimulating group II mGluR subtype 2 and 3 (mGluR2\/3) in the brainstem can decrease blood pressure and sympathetic nervous activity. Here, we hypothesized that the chronic stimulation of mGluR2\/3 in the dorsal medulla oblongata can alleviate hypertensive development via the modulation of autonomic nervous activity in young, spontaneously hypertensive rats (SHRs). Compared with that in the sham control group, chronic LY379268 application (mGluR2\/3 agonist; 0.40 \u03bcg\/day) to the dorsal medulla oblongata for 6 weeks reduced the progression of hypertension in 6-week-old SHRs as indicated by the 40 mmHg reduction in systolic blood pressure and promoted their parasympathetic nervous activity as evidenced by the heart rate variability. No differences in blood catecholamine levels or any echocardiographic indices were found between the two groups. The improvement of reflex bradycardia, a baroreflex function, appeared after chronic LY379268 application. The mRNA expression level of mGluR2, but not mGluR3, in the dorsal medulla oblongata was substantially reduced in SHRs compared to that of the control strain. In conclusion, mGluR2\/3 signaling might be responsible for hypertension development in SHRs, and modulating mGluR2\/3 expression\/stimulation in the dorsal brainstem could be a novel therapeutic strategy for hypertension via increasing the parasympathetic activity.<\/jats:p>","DOI":"10.1371\/journal.pone.0251495","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T17:47:18Z","timestamp":1621446438000},"page":"e0251495","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chronic stimulation of group II metabotropic glutamate receptors in the medulla oblongata attenuates hypertension development in spontaneously hypertensive rats"],"prefix":"10.1371","volume":"16","author":[{"given":"Julia Chu-Ning","family":"Hsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichi","family":"Sekizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Tochinai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-0560","authenticated-orcid":true,"given":"Masayoshi","family":"Kuwahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"pone.0251495.ref001","author":"World Health Organization","year":"2013","journal-title":"A global brief on hypertension: Silent killer, global public health crisis"},{"key":"pone.0251495.ref002","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1161\/HYPERTENSIONAHA.118.11609","article-title":"Prevalence of hypertension and cardiovascular risk according to blood pressure thresholds used for diagnosis","volume":"72","author":"JA Lamprea-Montealegre","year":"2018","journal-title":"Hypertension"},{"key":"pone.0251495.ref003","doi-asserted-by":"crossref","first-page":"e000473","DOI":"10.1136\/openhrt-2016-000473","article-title":"Amlodipine in hypertension: A first-line agent with efficacy for improving blood pressure and patient outcomes","volume":"3","author":"H Fares","year":"2016","journal-title":"Open Heart"},{"key":"pone.0251495.ref004","doi-asserted-by":"crossref","first-page":"78","DOI":"10.5688\/aj710478","article-title":"Physiology of the autonomic nervous system","volume":"71","author":"LK McCorry","year":"2007","journal-title":"Am J Pharm Educ"},{"key":"pone.0251495.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/S0100-879X1997000100001","article-title":"Glutamatergic transmission in the nucleus tractus solitarii: From server to peripherals in the cardiovascular information superhighway","volume":"30","author":"WT Talman","year":"1997","journal-title":"Braz J Med Biol Res"},{"key":"pone.0251495.ref006","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/01.HYP.38.3.549","article-title":"Role of the medulla oblongata in hypertension","volume":"38","author":"E Colombari","year":"2001","journal-title":"Hypertension"},{"key":"pone.0251495.ref007","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/S0006-8993(02)03260-2","article-title":"Cardiovascular responses to activation of metabotropic glutamate receptors in the nTS of the rat","volume":"952","author":"E Viard","year":"2002","journal-title":"Brain Res"},{"key":"pone.0251495.ref008","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnins.2011.00040","article-title":"Metabotropic glutamate receptors as novel therapeutic targets on visceral sensory pathways","volume":"5","author":"LA Blackshaw","year":"2011","journal-title":"Front Neurosci"},{"key":"pone.0251495.ref009","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0165-0173(98)00050-2","article-title":"Metabotropic glutamate receptors: electrophysiological properties and role in plasticity","volume":"29","author":"R. 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