{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:26:21Z","timestamp":1787358381972,"version":"build-2736575974"},"reference-count":79,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL153101"],"award-info":[{"award-number":["HL153101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL084207"],"award-info":[{"award-number":["HL084207"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL144807"],"award-info":[{"award-number":["HL144807"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL134850"],"award-info":[{"award-number":["HL134850"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK133121"],"award-info":[{"award-number":["DK133121"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23CDA1048244"],"award-info":[{"award-number":["23CDA1048244"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008980","name":"Medical College of Wisconsin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021528","name":"Advancing a Healthier Wisconsin Endowment","doi-asserted-by":"publisher","award":["AHW 5520639"],"award-info":[{"award-number":["AHW 5520639"]}],"id":[{"id":"10.13039\/100021528","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021528","name":"Advancing a Healthier Wisconsin Endowment","doi-asserted-by":"publisher","award":["5520879"],"award-info":[{"award-number":["5520879"]}],"id":[{"id":"10.13039\/100021528","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021528","name":"Advancing a Healthier Wisconsin Endowment","doi-asserted-by":"publisher","award":["AHW 5520631"],"award-info":[{"award-number":["AHW 5520631"]}],"id":[{"id":"10.13039\/100021528","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The endocrine renin-angiotensin system (RAS) is a key regulator of the autonomic nervous system and blood pressure (BP). Research over the past 5 decades has demonstrated that, in addition to this, circulating RAS tissues, including in the brain, express RAS components and have the capacity to generate and respond to angiotensin peptides. Recently, compelling new data have indicated the presence of renin expression within a discrete neuronal population in the nucleus ambiguus (NuAm), a brainstem region traditionally associated with parasympathetic control of heart rate (HR). These findings challenge conventional perspectives on brain RAS function and raise critical questions about its role in autonomic regulation. Here we provide a review of recent studies characterizing the NuAm and the adjacent C1 region of the rostral ventrolateral medulla (RVLM)\u2014a key vasomotor center linked to sympathetic outflow. We revisit the hypothesis that the NuAm may influence BP and HR through both parasympathetic and sympathetic pathways through interactions with the RVLM. Furthermore, we highlight an emerging trend of sex-dependent differences in brain RAS activation. Finally, we emphasize the need for targeted molecular and physiological investigations to clarify the interplay between the NuAm and RVLM, their respective contributions to autonomic balance, and the potential involvement of brain RAS dysfunction in neurogenic hypertension.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf134","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:43:18Z","timestamp":1755862998000},"source":"Crossref","is-referenced-by-count":1,"title":["Physiological and Molecular Implications of Angiotensinergic Signaling in the Brainstem"],"prefix":"10.1210","volume":"166","author":[{"given":"Mina","family":"Ghobrial","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Ariel","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Child Health Research Center, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L","family":"Grobe","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Cardiovascular Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Department of Biomedical Engineering, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curt D","family":"Sigmund","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Cardiovascular Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1887-7367","authenticated-orcid":false,"given":"Pablo","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Cardiovascular Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"issue":"6 Pt 2","key":"2026082120020120300_bqaf134-B1","first-page":"I4","article-title":"Circulating versus local renin-angiotensin system in cardiovascular homeostasis","volume":"77","author":"Dzau","year":"1988","journal-title":"Circulation"},{"issue":"1","key":"2026082120020120300_bqaf134-B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11906-019-1011-2","article-title":"The renin-angiotensin system in the central nervous system and its role in blood pressure regulation","volume":"22","author":"Nakagawa","year":"2020","journal-title":"Curr Hypertens Rep"},{"issue":"3","key":"2026082120020120300_bqaf134-B3","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1161\/HYPERTENSIONAHA.111.00356","article-title":"Angiotensin type 1a receptors in the subfornical organ are required for deoxycorticosterone acetate-salt hypertension","volume":"61","author":"Hilzendeger","year":"2013","journal-title":"Hypertension"},{"issue":"2 Pt 2","key":"2026082120020120300_bqaf134-B4","first-page":"H261","article-title":"Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats","volume":"251","author":"Itaya","year":"1986","journal-title":"Am J Physiol"},{"issue":"3","key":"2026082120020120300_bqaf134-B5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/cne.902700306","article-title":"Localization of angiotensin II receptor binding in rabbit brain by in vitro autoradiography","volume":"270","author":"Mendelsohn","year":"1988","journal-title":"J Comp Neurol"},{"issue":"1\u20132","key":"2026082120020120300_bqaf134-B6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0006-8993(96)01476-X","article-title":"Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats","volume":"750","author":"Fontes","year":"1997","journal-title":"Brain Res"},{"issue":"2 Pt 2","key":"2026082120020120300_bqaf134-B7","first-page":"I163","article-title":"The ventrolateral medulla. A new site of action of the renin-angiotensin system","volume":"11","author":"Andreatta","year":"1988","journal-title":"Hypertension"},{"issue":"5","key":"2026082120020120300_bqaf134-B8","doi-asserted-by":"crossref","first-page":"zqad043","DOI":"10.1093\/function\/zqad043","article-title":"Genetic ablation of prorenin receptor in the rostral ventrolateral medulla influences blood pressure and hydromineral balance in deoxycorticosterone-salt hypertension","volume":"4","author":"Mathieu","year":"2023","journal-title":"Function (Oxf)"},{"issue":"1","key":"2026082120020120300_bqaf134-B9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0006-8993(92)90551-J","article-title":"Angiotensin II excites vasomotor neurons but not respiratory neurons in the rostral and caudal ventrolateral medulla","volume":"577","author":"Li","year":"1992","journal-title":"Brain Res"},{"issue":"5 Pt 2","key":"2026082120020120300_bqaf134-B10","first-page":"R977","article-title":"Effect of angiotensin 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Ambiguus","volume":"82","author":"Fekete","year":"2025","journal-title":"Hypertension"},{"issue":"4 Pt 2","key":"2026082120020120300_bqaf134-B34","first-page":"724","volume":"34","author":"Mancia","year":"1999","journal-title":"Sympathetic Activation in the Pathogenesis of Hypertension and Progression of Organ Damage"},{"issue":"8","key":"2026082120020120300_bqaf134-B35","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/s41440-023-01335-6","article-title":"Clarification of hypertension mechanisms provided by the research of central circulatory regulation","volume":"46","author":"Kishi","year":"2023","journal-title":"Hypertens Res"},{"key":"2026082120020120300_bqaf134-B36","doi-asserted-by":"crossref","first-page":"123118","DOI":"10.1016\/j.lfs.2024.123118","article-title":"Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis","volume":"358","author":"Mi","year":"2024","journal-title":"Life 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disruption","volume":"791","author":"Duan","year":"2022","journal-title":"Neurosci Lett"},{"issue":"3","key":"2026082120020120300_bqaf134-B45","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1161\/HYPERTENSIONAHA.118.10921","article-title":"Rostral ventrolateral medulla and hypertension","volume":"72","author":"Guyenet","year":"2018","journal-title":"Hypertension"},{"issue":"3 Pt 2","key":"2026082120020120300_bqaf134-B46","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1161\/01.HYP.0000052944.54349.7B","article-title":"Ventrolateral medulla AT1 receptors support arterial pressure in Dahl salt-sensitive rats","volume":"41","author":"Ito","year":"2003","journal-title":"Hypertension"},{"issue":"22","key":"2026082120020120300_bqaf134-B47","doi-asserted-by":"crossref","first-page":"12305","DOI":"10.3390\/ijms222212305","article-title":"Angiotensin II and the cardiac parasympathetic nervous system in 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