Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium diet. Afferent renal denervation results in salt sensitive hypertension suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt sensitive hypertension is the endothelin B receptor (ETB-R) deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET-R blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high sodium diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26±3 to 9±3% and the PGE₂-mediated renal pelvic release of substance P from 9±1 and 3±1 pg/min. Conversely in rats fed low sodium diet, renal pelvic administration of the ETA-R antagonist BQ123 enhanced the ARNA response to increased renal pelvic pressure from 9±2% to 23±6% and the PGE₂-mediated renal pelvic release of substance P from 0±0 to 6±1 pg/min. Adding the ETA-R antagonist to ETB-R-blocked renal pelvises restored the responsiveness of renal sensory nerves in high sodium diet rats. Adding the ETB-R antagonist to ETA-R- blocked pelvises suppressed the responsiveness of the renal sensory nerves in low sodium diet rats. Conclusion: Activation of ETB-R and ETA-R contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high and low sodium intake, respectively. Impaired renorenal reflexes may contribute to the salt sensitive hypertension in the ETB-R deficient rat.