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

如果想从药理学上影响病理改变的肾脏传入神经活动，从而影响交感神经的控制，人们很快就会发现盐和钠的潜在作用。我们观察到，在盐依赖性DOCA高血压中，即使在静息状态下，肾自主神经系统也发生了病理改变（1,2）。当接受高盐饮食的正常大鼠通过所谓的背侧神经根切断术（Th12-L2）剥夺肾传入神经纤维时，盐依赖性动脉高血压发生(3)。免疫过程与慢性盐暴露和动脉高血压有关(4)。研究表明，免疫系统的激活，特别是在盐敏感性高血压(5)。在盐敏感的Dahl S大鼠中，高盐饮食增加肾淋巴细胞浸润和活性氧自由基形成，甚至在高血压合并肾损害发生之前（6,7）。在没有高血压的情况下，促炎发展可能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显示传入肾神经倾向于交感神经抑制性而不是兴奋性（8-11）。此外，促炎过程并非在所有情况下都作用于肾内传入神经末梢，而是经常以脱敏的方式（11-13）。从实际的角度来看，能够同时影响管周间质钠和促炎过程将是很有趣的，尤其是因为盐具有很强的免疫原性，如上所述。在这种情况下，钠-葡萄糖共转运体2 （SGLT2）可能非常重要，它是近端小管的特殊钠转运体，它的治疗影响最初是在糖尿病中，同时在心血管疾病中也起着非常重要的预防和治疗作用。

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).