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The presence of renin and angiotensinogen has been reported in the rostral ventrolateral medulla (RVLM). Overactivation of bulbospinal neurons in the RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRRRVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRRRVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRRRVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the \u201cmaintenance\u201d phase with a maximal peak at 13 d on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems.<\/jats:p>\n                  <jats:p>Graphical abstract<\/jats:p>","DOI":"10.1093\/function\/zqad043","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T16:35:09Z","timestamp":1691166909000},"source":"Crossref","is-referenced-by-count":5,"title":["Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension"],"prefix":"10.1152","volume":"4","author":[{"given":"Natalia M","family":"Mathieu","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M","family":"Fekete","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Vazirabad","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Gary C","family":"Mouradian","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Hodges","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Segar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-0873","authenticated-orcid":false,"given":"Justin L","family":"Grobe","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Cardiovascular Center, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Neuroscience Research Center, Medical College of Wisconsin , Milwaukee, WI 53226 , USA"},{"name":"Department of Biomedical Engineering, Medical College of Wisconsin , Milwaukee, WI 53226 , 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