Opposite Arterial Pressure Responses to Renal Afferent Nerve Stimulation in Unanesthetized Versus Anesthetized Rats: Implications for the Neural‐Renal Axis and Hypertension

Abstract

Neural control of the kidney remains a primary focus of treatment of cardiovascular and renal disease, including hypertension (HTN). Moreover, recent studies support a role of renal afferent nerves in the modulation of sympathetic nerve activity (SNA), and in turn, arterial pressure (AP). We recently reported resting afferent nerve activity (ARNA) is elevated in the DOCA‐salt hypertensive rat, and that targeted afferent renal nerve ablation attenuates this model of hypertension (Banek et al. Hypertension 2016). These findings suggest that increased ARNA contributes to the pathogenesis of HTN. Previous investigations of the responses of AP and SNA to renal afferent nerve stimulation have been conducted in anesthetized animals have reported a sympatho‐inhibitory response. The present study was designed to measure the acute AP response to increased ARNA in anesthetized and unanesthetized preparations. Male Sprague Dawley rats (300–400g) underwent acute renal afferent stimulation while under 2% isoflurane anesthesia (ISO; n=12) or in the absence of anesthesia following a cortical decerebration (DEC; n=12). Animals were instrumented to measure AP, heart rate (HR), and ARNA. To activate renal afferent nerves, a ureteral catheterization was performed to perfuse the renal pelvis with vehicle 0.9% saline [VEH] or with the TRPV1‐agonist 50μM capsaicin (CAP). Following instrumentation and a 30‐minute stabilization period, ARNA and cardiovascular responses to VEH or CAP stimulation were recorded. Peak responses in ARNA, AP, and HR were quantified and compared between ISO vs. DEC preparations by a Student's t‐test (α=.05). ARNA responses were calculated as percent change from baseline (%ARNA). Data presented as mean±SEM. There was no difference in resting ∫ARNA, AP, or HR prior to afferent stimulation between ISO and DEC groups. VEH perfusion of the renal pelvis elicited no response in both ISO and DEC groups. In contrast, CAP administration resulted in marked increase in %ARNA that was similar in magnitude in both groups (ISO 214±31% vs. DEC 239±40%). More importantly, whereas the CAP‐induced increase in ARNA elicited a depressor response in ISO rats (−17±6mmHg), CAP evoked an opposing pressor response in DEC rats (+54±9mmHg). These findings suggest the existence of a renal afferent nerve‐dependent sympatho‐excitatory reflex in the rat, and anesthesia may directly interfere in this signaling pathway. It is important to note it is unknown whether this acute reflex translates to long‐term regulation of SNA and AP. While the anatomical and biological mechanisms of this reflex remain rudimentary, further studies are underway to chronically monitor afferent nerve activity and blood pressure in conscious freely moving rats to elucidate this important neural‐renal axis.Support or Funding InformationNIH 5R01HL116476; NIH 2T32HL7741