Impaired renal sympathoinhibitory responses to vagal afferent stimulation in chronic kidney disease

Background: Cardiopulmonary afferents within the vagus nerve contribute to the reflex control of sympathetic outflow in response to changes in thoracic blood volume and pressures. There is evidence that stimulation of vagal afferents evokes reduced sympathoinhibitory responses in hypertensive conditions. Objective: To assess the effect of vagal afferent nerve stimulation on sympathetic outflow in a hypertensive cystic kidney disease rat model. Methods: In urethane anaesthetised male Lewis Polycystic Kidney (LPK) and Lewis control rats, changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in response to vagal afferent stimulation (5-second train, 4.0V, 2.0-ms pulses, at 1, 2, 4 and 8 Hz) were recorded. Results: Compared to Lewis, LPK rats showed higher resting HR (350 ± 8 vs. 390 ± 14 bpm, P≤0.01), systolic blood pressure (SBP, 118 ± 6 vs. 178 ± 6 mmHg, P < 0.0001) and RSNA (2.6 ± 0.5 vs. 5.1 ± 1.0 μV, P < 0.05). Electrical stimulation of the cervical vagal afferent nerves produced frequency-dependent reductions in MAP, HR and RSNA in all experimental groups. Decreases in MAP and HR were comparable in the LPK and Lewis. In contrast, smaller reductions in RSNA were observed in the LPK relative to Lewis at both 4 and 8 Hz (P < 0.01). Conclusions Reflex inhibition of RSNA, but not HR and MAP, is impaired in the LPK. An inability to reflexly inhibit sympathetic outflow to the kidney may contribute to the altered blood pressure homeostasis observed in kidney disease. Future studies will investigate if sympathoinhibitory responses to vagal afferent stimulation are impaired earlier in the course of disease progression.