TRPV1 blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal injury in rats

Renal injury is associated with inflammatory responses within the kidney which could involve activation of transient receptor potential vanilloid 1 (TRPV1) channels. This study investigated whether TRPV1 channels modulate baroreflex regulation of renal sympathetic nerve activity (RSNA) in a rat model of cisplatin-mediated renal injury. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA 4 days after a single i.p. dose of cisplatin (5 mg kg⁻¹). RSNA and HR baroreflex gain curves (BRC) were generated and the decrease in RSNA to volume expansion was determined during intrarenal capsazepine (CPZ, 15 µg kg⁻¹ h⁻¹) infusion. In the cisplatin group (MAP: 85 ± 13 mmHg; HR: 328 ± 17 bpm; RSNA: 0.83 ± 0.41 µV s), the slope and maximum gain of the BRC were approximately 50% lower (P = 0.015–0.033) than the control group (MAP: 78 ± 12 mmHg; HR: 352 ± 27 bpm; RSNA: 0.57 ± 0.36 µV s). Intrarenal CPZ infusion in the cisplatin group restored the slope (0.15 ± 0.04 vs. 0.09 ± 0.02, P = 0.014) of the RSNA BRC to near normal values. The RSNA response to volume expansion in the cisplatin group was enhanced following CPZ compared to vehicle infusion (−24 ± 14% vs. 1.7 ± 39%, P = 0.015). Intrarenal tumour necrosis factor α (TNF-α) infusion (2 µg kg⁻¹ h⁻¹) in normal rats decreased the slope of the BRC by 40% (P = 0.035) compared to vehicle infusion, which was slightly enhanced following intrarenal CPZ infusion. These findings demonstrate that TRPV1 channels contribute to the depressed baroreceptor control of RSNA in renal injury. Furthermore, the action of TNF-α in disrupting the baroreflex control mechanism partially involves TRPV1 channels.