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

• Applicants: Professorin Dr. Kerstin Amann; Professor Dr. Roland Veelken
• Subject Area: Nephrology ; Anatomy and Physiology
• Term: since 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 248553778

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).

• DFG Programme: Research Grants