ReviewChronic kidney disease impairs renal nerve and haemodynamic reflex responses to vagal afferent input through a central mechanism

•Impaired reflex control of autonomic outflows is a hallmark of autonomic dysfunction in CKD.•Altered central processing of vagal afferent input could underlie autonomic dysfunction in CKD.•We demonstrated impaired central integration of vagal afferent neurotransmission in CKD.•Central deficits promoted differential deteriorations in autonomic outflows to the kidney, heart and vasculature.•A critical involvement of a new central mechanism in the pathogenesis of autonomic dysfunction in CKD was recognized.

We investigated age- and sex-related changes in reflex renal sympathetic nerve activity (RSNA) and haemodynamic responses to vagal afferent stimulation in a rodent model of chronic kidney disease (CKD). Using anaesthetised juvenile (7-8 weeks) and adult (12-13 weeks) Lewis Polycystic Kidney (LPK) and Lewis control rats of either sex (n = 63 total), reflex changes in RSNA, heart rate (HR) and mean arterial pressure (MAP) to vagal afferent stimulation (5-s train, 4.0 V, 2.0-ms pulses, 1-16 Hz) were measured. In all groups, stimulation of the vagal afferents below 16 Hz produced frequency-dependent reductions in RSNA, HR and MAP, while a 16 Hz stimulus produced an initial sympathoinhibition followed by sympathoexcitation. In juvenile LPK versus age-matched Lewis, sympathoinhibition was reduced when responses were expressed as % baseline (P < 0.05), but not as microvolts, while bradycardic responses were greater. Reflex depressor responses were greater (P = 0.015) only in juvenile female LPK. In adult LPK, reflex sympathoinhibition (%) was blunted (P < 0.05), and an age-related decline apparent (when expressed as microvolts). Reflex reductions in HR and MAP were only diminished (P < 0.05) in adult female LPK versus age-matched Lewis. Peak reflex sympathoexcitation at 16 Hz did not differ between groups; however, area under the curve values were greater in the LPK versus Lewis (overall, 9 ± 1 versus 19 ± 3 μV s, P < 0.05) irrespective of age, suggestive of enhanced sympathoexcitatory drive in the LPK. Our data demonstrates a progressive deficit in the central processing of vagal afferent input and a differential sex influence on reflex regulation of autonomic function and blood pressure homeostasis in CKD.