Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA071

Poster Communications

Role of renal afferent nerves in injury and inflammation of the kidney

E. Murphy1, L. Mulcahy1, M. Abdulla1

1. Department of Physiology, University College Cork, Co.Cork, Ireland.

Renal inflammation is associated with deranged cardiovascular homeostasis leading to hypertension. Inflammatory cytokines such as TNF-α play a key role in initiating responses from the diseased kidney which ultimately results in dysregulation of blood pressure control mechanisms. Male Wistar rats (275-350g, n=23) were anaesthetised with α-chloralose: urethane anaesthesia (3ml kg-1) and the right femoral artery and vein were cannulated to allow measurement of mean arterial pressure (MAP) and heart rate (HR), and infusion of saline and supplemental anaesthetic. The right kidney was exposed via a flank incision and a cannula was inserted into renal corticomedullary border to allow infusion of saline, TNF-α (2µg kg-1 h-1) or capsazepine (CPZ), a TRPV1 blocker at 17 ml min-1. Animals were allowed to stabilise for ~45 minutes. Experimental protocol comprised two phases during which intrarenal infusions of either saline or a drug was done. During each phase, a baroreflex gain curve was generated by I.V. phenylephrine and sodium nitroprusside (50µg kg-1 min-1) to increase and decrease blood pressure, respectively. In a group of rats, the renal nerve activity from the ipsilateral kidney was blocked by perfusing lidocaine (5%), a local anaesthetic on the renal artery at 17 ml min-1 for 10 minutes using a small diameter cannula. A renal nerve bundle running close to the renal artery of the contralateral kidney was dissected free from connective tissues, placed on bipolar electrodes and used to record renal sympathetic nerve activity (RSNA). At the end of the experiment, the animals were euthanised and the background noise was recorded. Data were expressed as mean ± S.E.M. and compared using student's t-test and ANOVA with significance at P<0.05. Intrarenal infusion of TNF-α blunted (P=0.005) the sensitivity of the baroreflex by almost 65% (0.09±0.04 vs. 0.25±0.01 μV.s mmHg-1). However, when TNF-α was infused intrarenally following nerve activity blockade by lidocaine there was an approximate 75% increase (P=0.06) in the sensitivity of the baroreflex. The blunted sensitivity of the baroreflex to intrarenal TNF-α was restored to near normal levels (P=0.025) when TNF-α was infused in the presence of a background infusion of CPZ (0.20±0.04 vs. 0.10±0.02 μV.s mmHg-1). The results from this study indicate that TNF-α, a pro-inflammatory mediator evokes a renal nerve-mediated response that adds to a blunted baroreflex control mechanism. This suggests that in renal injury and disease the generation of inflammatory cytokines has the potential of initiating activity within the renal afferent nerves which can ultimately modulate the blood pressure control mechanism.

Where applicable, experiments conform with Society ethical requirements