Chronic kidney disease is associated with cardiovascular autonomic dysfunction. In a rat model of autosomal recessive cystic kidney disease, we have previously shown impaired cardiac baroreflex function and sympathetic overactivity, but intact baroreflex control of the splanchnic sympathetic nerve. The present study aimed to further investigate the baroreflex pathway by examining both the sensory afferent component of the baroreflex arc and baroreflex control of a different sympathetic nerve bed, the renal nerve. In urethane anaesthetised Lewis polycystic kidney (LPK) and Lewis control rats (total n=20), changes in aortic depressor nerve activity (ADNA) and renal sympathetic nerve activity (RSNA) in response to phenylephrine (10–50 µg/kg)- and sodium nitroprusside (50–70 µg/kg)-induced alterations in mean arterial pressure (MAP) were recorded. The MAP-nerve activity relationship was characterized using a four-parameter sigmoid regression. Compared to Lewis control, LPK rats had significantly higher resting heart rate (HR, 351±7 vs 414±10 beats per minute, P<0.0001), systolic blood pressure (SBP, 113±4 vs 174±8 mm Hg, P<0.0001) and RSNA (3.5±0.5 vs 6.6±0.8 µV, P=0.001) but comparable ADNA (0.9±0.2 vs 1.0±0.3 µV). The ADNA barocurve was comparable in LPK and Lewis rats but shifted rightward in the LPKs, suggesting an intact sensory afferent pathway that is operational at higher resting MAP. The RSNA baroreflex function curve was shifted to the right towards higher MAP range; but there was a marked reduction in the gain (P=0.0003) and the magnitude of reflex sympathoinhibition (P=0.005), indicating impaired baroreflex control of RSNA. We conclude that unlike baroreflex control of the splanchnic nerve, baroreflex control of RSNA is impaired in the LPK model, indicative of differential perturbations in sympathetic outflow to distinct effector organs. Furthermore, results suggest that impaired sympathetic baroreflexes are due to altered central and/or efferent mechanisms rather than a defect in the sensory afferent pathway of the reflex.