Stimulation of afferent renal nerves under physiological and pathological conditions: is there any possibility of pharmacological intervention?

生理和病理条件下传入肾神经的刺激：是否有药物干预的可能性？

• 批准号: 248553778
• 负责人: Professorin Dr. Kerstin Amann
• 金额: --
• 依托单位: Pathologisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/248553778?language=en
• 关键词: Stimulation; afferent; renal; nerves; under

If one looks for ways to pharmacologically influence pathologically altered afferent nervous activity from the kidney that might affect sympathetic control, one relatively quickly encounters the potential role of salt and sodium. It was observed that in salt-dependent DOCA hypertension, even under resting conditions, the renal autonomic nervous system was pathologically altered (1, 2). When normal rats receiving high-salt diet are deprived of their renal afferent nerve fibers via a so-called dorsal rhizotomy (Th12-L2), salt-dependent arterial hypertension develops (3). Immunologic processes are involved in chronic salt exposure and arterial hypertension (4). Studies indicate activation of the immune system, particularly in salt-sensitive hypertension (5). In salt-sensitive Dahl S rats, a high-salt diet increased renal lymphocyte infiltration and reactive oxygen radical formation even before established hypertension with renal damage had developed (6, 7). Proinflammatory developments already in the absence of hypertension are likely to further limit the sensitivity of afferent renal nerve pathways leading to sympathoinhibition: first, our own preliminary data show that afferent renal nerves tend to be sympathoinhibitory rather than - excitatory (8-11). Furthermore, proinflammatory processes were shown to act on intra-renal afferent nerve endings not under all circumstances but frequently in a desensitizing manner (11-13). From a practical point of view, it would thus be interesting to be able to influence both peritubular-interstitial sodium and proinflammatory processes simultaneously, not least because salt has a strong immunogenic potency, as outlined above. In this context, special sodium transporters of the proximal tubules, whose therapeutic influenceability initially in diabetes mellitus and meanwhile quite generally in cardiovascular diseases play a very important preventive and curative role, could be of great importance: the sodium-glucose co-transporters 2 (SGLT2).

如果人们寻找方法来阻止可能影响交感神经控制的来自肾脏的病理改变的传入神经活动，人们相对较快地遇到了盐和钠的潜在作用。据观察，在盐依赖性DOCA高血压中，即使在静息条件下，肾自主神经系统也发生病理改变（1，2）。当接受高盐饮食的正常大鼠通过所谓的背根切断术（Th 12-L2）被剥夺其肾传入神经纤维时，盐依赖性动脉高血压发展（3）。免疫过程参与慢性盐暴露和动脉高血压（4）。研究表明免疫系统的激活，特别是在盐敏感性高血压中（5）。在盐敏感的Dahl S大鼠中，高盐饮食增加了肾淋巴细胞浸润和活性氧自由基形成，甚至在建立高血压伴肾损伤之前就已经出现（6，7）。在没有高血压的情况下，促炎性发展可能会进一步限制传入肾神经通路的敏感性，导致交感神经抑制：首先，我们自己的初步数据表明，传入肾神经倾向于交感神经抑制，而不是兴奋（8-11）。此外，促炎过程显示作用于肾内传入神经末梢，但不是在所有情况下，而是经常以脱敏方式（11-13）。从实践的角度来看，能够同时影响管周间质钠和促炎过程将是令人感兴趣的，尤其是因为盐具有如上所述的强免疫原性效力。在这种情况下，近端小管的特殊钠转运蛋白可能非常重要：钠-葡萄糖共转运蛋白2（SGLT 2），其最初在糖尿病中的治疗影响能力，同时在心血管疾病中发挥非常重要的预防和治疗作用。

项目成果

Retinal microperfusion after renal denervation in treatment-resistant hypertensive patients

难治性高血压患者肾去神经术后视网膜微灌注

• DOI: 10.1007/s00392-015-0845-0
• 发表时间: 2015
• 期刊: Clinical Research in Cardiology
• 影响因子: 5
• 作者: Harazny JM;Schmid A;Ditting T;Veelken R;Bladowski M;Michelson G;Uder M;Schmieder RE
• 通讯作者: Schmieder RE

Impact of renal denervation on tissue Na+ content in treatment-resistant hypertension

肾去神经支配对难治性高血压患者组织钠含量的影响

• DOI: 10.1007/s00392-017-1156-4
• 发表时间: 2018
• 期刊: Clinical Research in Cardiology
• 影响因子: 5
• 作者: Kopp C;Dahlmann A;Schmid A;Linz P;Cavallaro A;Hammon M;Ditting T;Veelken R;Uder M;Titze J;Schmieder RE
• 通讯作者: Schmieder RE

Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension

• DOI: 10.1097/hjh.0000000000000556
• 发表时间: 2015-06-01
• 期刊: JOURNAL OF HYPERTENSION
• 影响因子: 4.9
• 作者: Ott, Christian;Mahfoud, Felix;Schmieder, Roland E.
• 通讯作者: Schmieder, Roland E.

The effect of renal denervation in moderate treatment-resistant hypertension with confirmed medication adherence

• DOI: 10.1097/hjh.0000000000001110
• 发表时间: 2016-12-01
• 期刊: JOURNAL OF HYPERTENSION
• 影响因子: 4.9
• 作者: Ott, Christian;Mahfoud, Felix;Schmieder, Roland E.
• 通讯作者: Schmieder, Roland E.

Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging

• DOI: 10.1007/s00270-015-1192-2
• 发表时间: 2016-03
• 期刊: CardioVascular and Interventional Radiology
• 影响因子: 2.9
• 作者: A. Schmid;R. Schmieder;M. Lell;R. Janka;R. Veelken;R. Schmieder;M. Uder;C. Ott