The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses
The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses
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肾去神经支配后，在不同强度的血压反应的引导下，肾内血压调节系统发生差异性改变
DOI：
10.1038/s41440-022-01047-3
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发表时间：
2022
影响因子：
5.4
通讯作者：
Y. Yin
中科院分区：
文献类型：
--
作者：
Yinchuan Lai;Hao Zhou;Weijie Chen;Hang Liu;Guangliang Liu;Yan;Huaan Du;Bo Zhang;Yidan Li;Kamsang Woo;Y. Yin
本研究的目的是调查肾神经刺激（RNS）引导的肾去神经支配（RDN）后肾内血压（BP）调节系统的变化。 21 只狗被随机分配到 RNS 确定的强血压升高反应位点（SRA 组，n = 7）或弱（WRA 组，n = 7）接受 RDN，或仅接受 RNS（RNS 对照，RSC，n = 7）。随访4周后，通过免疫组织化学分析评估肾交感神经成分、肾素-血管紧张素系统（RAS）主要成分以及参与钠和水重吸收的主要转运蛋白。与RSC治疗相比，RDN治疗显着降低肾脏去甲肾上腺素和酪氨酸羟化酶水平，降低肾素含量并抑制血管紧张素原的现场生成。此外，在WRA和SRA组中，兴奋轴成分的表达下调，包括血管紧张素转换酶（ACE）、血管紧张素II和血管紧张素II 1型受体，而心血管系统的保护性轴成分，包括ACE2和Mas受体的表达上调。此外，RDN 降低了肾脏中水通道蛋白 1 和水通道蛋白 2 的丰度。尽管 RDN 对 NKCC2 整体表达的影响很小，但其激活 (p-NKCC2) 和顶膜定向富集 (mNKCC2) 显着减弱。所有这些变化在SRA组中比WRA组更明显。 RNS引导的选择性RDN通过影响肾脏神经激素系统以及钠和水转运系统，有效降低全身血压，并且这些作用在血压反应强烈的部位更为优越。
The aim of this study was to investigate alterations in the intrarenal blood pressure (BP) regulation system after renal denervation (RDN) guided by renal nerve stimulation (RNS). Twenty-one dogs were randomized to receive RDN at strong (SRA group, n = 7) or weak (WRA group, n = 7) BP-elevation response sites identified by RNS or underwent RNS only (RNS-control, RSC, n = 7). After 4 weeks of follow-up, renal sympathetic components, the main components of renin-angiotensin system (RAS) and the major transporters involved in sodium and water reabsorption were assessed by immunohistochemical analysis. Compared with RSC treatment, RDN therapy significantly reduced renal norepinephrine and tyrosine hydroxylase levels, decreased the renin content and inhibited the onsite generation of angiotensinogen. Moreover, the expression of exciting axis components, including angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II type-1 receptor, was downregulated, while protective axis components for the cardiovascular system, including ACE2 and Mas receptors, were upregulated in both WRA and SRA groups. Moreover, RDN reduced the abundance of aquaporin-1 and aquaporin-2 in kidneys. Although RDN had a minimal effect on overall NKCC2 expression, its activation (p-NKCC2) and directional enrichment in the apical membrane (mNKCC2) were dramatically blunted. All these changes were more obvious in the SRA group than WRA group. Selective RDN guided by RNS effectively reduced systemic BP by affecting the renal neurohormone system, as well as the sodium and water transporter system, and these effects at sites with a strong BP response were more superior.
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影响因子：
15.9
作者：
Gonzalez-Villalobos, Romer A.;Janjoulia, Tea;McDonough, Alicia A.
通讯作者：
McDonough, Alicia A.
影响因子：
19.6
作者：
L. Navar
通讯作者：
L. Navar
影响因子：
19.6
作者：
Ferrario, CM;Jessup, J;Chappell, MC
通讯作者：
Chappell, MC
影响因子：
24
作者：
Kiuchi MG;Esler MD;Fink GD;Osborn JW;Banek CT;Böhm M;Denton KM;DiBona GF;Everett TH 4th;Grassi G;Katholi RE;Knuepfer MM;Kopp UC;Lefer DJ;Lohmeier TE;May CN;Mahfoud F;Paton JFR;Schmieder RE;Pellegrino PR;Sharabi Y;Schlaich MP
通讯作者：
Schlaich MP
影响因子：
4.8
作者：
Mutig, Kerim;Kahl, Thomas;Bachmann, Sebastian
通讯作者：
Bachmann, Sebastian