Renal failure and injury are associated with inflammatory responses within the kidney which could be mediated through transient receptor potential vanilloid type 1 (TRPV1) receptors. This study investigated whether TRPV1 receptors contribute to the modulation of high-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) in cisplatin induced renal failure rats. Wistar rats (300-350g) were divided into a renal failure (RF, n=7) or control (C, n=7) group which received IP either cisplatin (5mg/kg) or saline (0.9% NaCl), respectively, 4 days before the acute study. Rats were anaesthetised with chloralose:urethane mixture (1ml, 16.5:250mg/ml, IP). Cannulae were inserted into the right femoral artery, for mean arterial pressure (MAP) and heart rate (HR) measurement, and vein for saline (3ml/h) infusion. The right kidney was exposed and a small cannula inserted 4.5mm into the rostral pole of the kidney to lie at the corticomedullary border for intrarenal infusion of saline or a TRPV1 blocker capsazepine (CPZ). The left kidney was exposed, a renal sympathetic nerve bundle was dissected and sealed onto recording electrodes. After 2h stabilisation, baroreflex gain curves were generated using IV phenylephrine and sodium nitroprusside (50µg/kg/min). Saline (1ml/h) was infused into the right kidney 20min before, and during the first baroreflex gain curve was generated and then CPZ (5µg/ml) was infused (1ml/h) for 20min before, and during the second baroreflex challenge 2hr after the first baroreflex curve. The animal was euthanized at the end of the experiment and the background noise obtained. Data, mean±SEM were compared using t-test with significance at P<0.05. In C, the MAP, HR and RSNA values measured during CPZ infusion were not different from their respective values before CPZ (84±5 vs. 83±5 mmHg, 405±16 vs. 399±16 bpm, 0.68±0.15 vs. 0.65±0.14 µV.s, respectively). Similarly, in RF, the MAP, HR and RSNA were similar to their respective values before CPZ (94±5 vs. 94±5 mmHg, 379±12 vs. 382±10 bpm, 0.82±0.19 vs. 0.75±0.16 µV.s, respectively). In RF, the slope of the baroreflex curve of RSNA following saline infusion was significantly smaller than C (RF vs. C; 0.09±0.01 vs. 0.15±0.02, P<0.05). The intrarenal infusion of CPZ in C had no effect on the slope of the baroreflex curve (CPZ vs. Saline; 0.14±0.01 vs. 0.15±0.02). However, in RF, the slope of the baroreflex curve increased significantly following CPZ (CPZ vs. Saline; 0.17±0.02 vs. 0.09±0.01, P<0.05). These findings demonstrate that normally TRPV1 receptors have little influence on the baroreflex gain curves. However, in renal failure there is an attenuation of the sensitivity of the baroreflex gain curve which is mediated via TRPV1 receptors as it can be normalised by blockade of TRPV1 receptors.