Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.
Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.
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去氧皮质酮-盐性高血压患者延髓头端腹外侧原肾素受体基因缺失对血压和水矿物质平衡的影响。
DOI：
10.1093/function/zqad043
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发表时间：
2023
期刊：
影响因子：
6.2
通讯作者：
Nakagawa, Pablo
中科院分区：
文献类型：
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作者：
Mathieu, Natalia M.;Fekete, Eva M.;Muskus, Patricia C.;Brozoski, Daniel T.;Lu, Ko-Ting;Wackman, Kelsey K.;Gomez, Javier;Fang, Shi;Reho, John J.;Grobe, Connie C.;Vazirabad, Ibrahim;Mouradian Jr, Gary C.;Hodges, Matthew R.;Segar, Jeffrey L.;Grobe, Justin L.;Sigmund, Curt D.;Nakagawa, Pablo
关键词：
非酶激活的肾素通过其与原肾素受体（PRR）的相互作用已被认为是一个关键的机制，局部肾素-血管紧张素系统（RAS）激活。在延髓头端腹外侧区（RVLM）存在肾素和血管紧张素原。RVLM中球脊髓神经元的过度激活与高血压（HTN）有关。以往的研究表明，脑RAS在脱氧皮质酮（DOCA）-盐HTN模型的发病机制中起作用。因此，我们假设RVLM中的PRR参与RAS的局部激活，促进DOCA盐HTN的发展。靶向RVLM的选择性PRR消融（PRRRVLM-HTN小鼠）在DOCA盐HTN中产生了意想不到的性别依赖性和双相表型。也就是说，PRRRVLM-HTN雌性动物（而非雄性动物）在DOCA-盐HTN的初始阶段表现出达到最大升压反应的显著延迟。雌性PRRRVLM-ESTA随后表现出加剧DOCA盐诱导的升压反应在“维持”阶段与最大峰值在13天的DOCA盐。这种加重的反应与对阻力小动脉和肾脏的交感神经驱动增加、响应于DOCA盐的液体和钠摄入和输出加重以及诱导液体从细胞内向细胞外空间的动员伴随加压素升高相关。PRR的消融抑制了参与RVLM中RAS激活和儿茶酚胺合成的基因，但也诱导了参与炎症反应的基因的表达。这项研究说明了复杂的和性别依赖性的作用，PRR的神经控制BP和水矿物平衡，通过自主神经和神经内分泌系统。图形摘要
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 (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 “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
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影响因子：
8.3
作者：
Mathieu, Natalia M.;Nakagawa, Pablo;Grobe, Connie C.;Reho, John J.;Brozoski, Daniel T.;Lu, Ko-Ting;Wackman, Kelsey K.;Ritter, McKenzie L.;Segar, Jeffrey L.;Grobe, Justin L.;Sigmund, Curt D.
通讯作者：
Sigmund, Curt D.
DOI：
10.1007/s00424-021-02598-z
发表时间：
2021-08
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Figueiredo M;Daryadel A;Sihn G;Müller DN;Popova E;Rouselle A;Nguyen G;Bader M;Wagner CA
通讯作者：
Wagner CA
影响因子：
8.3
作者：
Belanger, Kasey M.;Crislip, G. Ryan;Sullivan, Jennifer C.
通讯作者：
Sullivan, Jennifer C.
DOI：
10.1152/ajpheart.00473.2018
发表时间：
2019-03-01
影响因子：
4.8
作者：
Gatineau, Eva;Cohn, Dianne M.;Yiannikouris, Frederique
通讯作者：
Yiannikouris, Frederique
影响因子：
4.8
作者：
Kissing, Sandra;Hermsen, Christina;Saftig, Paul
通讯作者：
Saftig, Paul