Renal nerve afferents drive preferential renal sympathoexcitation in response to acute renal ischemia/reperfusion in rats

Abstract

Renal nerve activity is composed of afferent (sensory) and efferent (sympathetic) nerve activity. Ischemia/reperfusion (IR) of the kidney increases renal sympathetic nerve activity (rSNA) and depresses renal function. As the role of renal afferent fibers in acute renal IR is unclear, we tested the hypothesis that renal IR increases rSNA triggered by renal afferent nerves responding to acute ischemia. Two experimental series were performed in adult male Wistar rats. IR was induced by total obstruction of blood flow to the left kidney by clamping the renal artery for 60 min and reperfusion for 120 min. We recorded MAP, HR, rSNA, and splanchnic sympathetic vasomotor activity (sSNA) in 8 normal IR rats and 6 left kidney deafferented IR rats (IR ARD). Renal deafferentation was performed using capsaicin administration to the left renal nerve 2 weeks before the experiments. Blood samples were collected before ischemia and at the end of reperfusion for total and differential leukocyte counts. Renal ischemia significantly increased rSNA 23 % (20 min: 0,07 ± 0,04mVs P < 0.05) but not sSNA. The increase in rSNA was triggered by activation of renal afferent fibers, since IR significantly reduced rSNA in the IR ARD group maximal decrease in frequency 22 % (180 min: −62 ± 29Δspikes/s) and in amplitude 41 % (−0,29 ± 0, 12mVs, P < 0.05) and induced hypotension and bradycardia. However, no significant difference was observed between groups in blood leukocyte profile, but a significant reduction in renal IL-6 was found in IR ARD, suggesting a reduction in renal inflammation in deafferented IR rats. The results show that renal afferent nerves trigger a preferential increase in rSNA and inflammation in the kidney during acute IR.