TRPV1-expressing C-fiber afferents preferentially drive renal sympathetic nerve activity in response to acute administration of low-dose furosemide in rats.

This study investigates the role of renal nerve afferents in sympathetic vasomotor responses during acute low-dose furosemide administration intravenously or directly in the renal pelvis. We hypothesized that furosemide activates renal nerve afferents, modulating sympathetic vasomotor activity. To test this hypothesis, we conducted simultaneous recordings of renal sympathetic nerve activity (rSNA) and splanchnic sympathetic nerve activity (sSNA) in Wistar rats. The effects of intravenous furosemide infusion (1 mg/kg/h) on mean arterial pressure, heart rate, rSNA, and sSNA in control (CTRL, n = 5) and afferent renal denervated rats (ARD, n = 5) were investigated. In addition, we infused furosemide (from 10 to 100 µg/mL; 200 µL) directly in the renal pelvis (n = 8), with simultaneous recordings of hemodynamic parameters and sympathetic nerve activity. Furosemide induced a significant reduction in rSNA (spikes/s) but not in sSNA in the ARD compared with the CTRL group (rSNA maximal decrease of 21 ± 7 in ARD vs. a maximal increase of 27 ± 13 spikes/s in CTRL at 120 min, *P < 0.05), as well as in the amplitude of bursts (rSNA -0.21 ± 0.072 vs. 0.062 ± 0.16 mVs at 120 min, *P < 0.05). Moreover, intrapelvic furosemide infusion in CTRL rats preferentially increased rSNA (69% of the maximal response induced by capsaicin); as for sSNA, there was no significant difference. These findings suggest that transient receptor potential vanilloid type-1-expressing C-fiber afferents, located in the renal pelvis, are activated by furosemide, leading to a preferential change in the pattern of sympathetic activity to the kidneys, independently of blood volume depletion.NEW & NOTEWORTHY Afferent nerves from the renal pelvis contribute to the modulation of renal sympathetic nerve activity (rSNA) in response to low-dose furosemide intravenous administration. Capsaicin-sensitive C-fiber afferents, located in the renal pelvis, selectively alter the pattern of sympathetic outflow to the kidneys. Intrapelvic low-dose furosemide increases rSNA without affecting splanchnic sympathetic nerve activity (sSNA).