دورية أكاديمية
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Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.

التفاصيل البيبلوغرافية
العنوان: Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.
المؤلفون: Mathieu NM; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Fekete EM; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Muskus PC; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Brozoski DT; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Lu KT; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Wackman KK; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Gomez J; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Fang S; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Reho JJ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Grobe CC; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Vazirabad I; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Mouradian GC Jr; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Hodges MR; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Segar JL; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Grobe JL; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Sigmund CD; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Nakagawa P; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
المصدر: Function (Oxford, England) [Function (Oxf)] 2023 Aug 07; Vol. 4 (5), pp. zqad043. Date of Electronic Publication: 2023 Aug 07 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101770668 Publication Model: eCollection Cited Medium: Internet ISSN: 2633-8823 (Electronic) Linking ISSN: 26338823 NLM ISO Abbreviation: Function (Oxf) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Oxford, UK] : Oxford University Press, [2020]-
مواضيع طبية MeSH: Desoxycorticosterone Acetate* , Hypertension*/genetics , Prorenin Receptor*/genetics, Animals ; Female ; Mice ; Blood Pressure ; Receptors, Cell Surface ; Renin/genetics ; Sodium Chloride ; Vasoconstrictor Agents
مستخلص: Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. 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 (PRR RVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRR RVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRR RVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the "maintenance" 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. Graphical abstract.
Competing Interests: There is no conflict to report.
(© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society.)
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معلومات مُعتمدة: K01 HL153101 United States HL NHLBI NIH HHS; P01 HL014388 United States HL NHLBI NIH HHS; P01 HL084207 United States HL NHLBI NIH HHS; R35 HL144807 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Atp6ap2; DOCA-salt hypertension; autonomic function; blood pressure; hypertension; prorenin receptor; renin–angiotensin system; rostral ventrolateral medulla; sex-difference; sympathetic nervous system
المشرفين على المادة: 6E0A168OB8 (Desoxycorticosterone Acetate)
0 (Prorenin Receptor)
0 (Receptors, Cell Surface)
EC 3.4.23.15 (Renin)
451W47IQ8X (Sodium Chloride)
0 (Vasoconstrictor Agents)
تواريخ الأحداث: Date Created: 20230823 Date Completed: 20230830 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC10440998
DOI: 10.1093/function/zqad043
PMID: 37609445
قاعدة البيانات: MEDLINE
الوصف
تدمد:2633-8823
DOI:10.1093/function/zqad043