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

Abstract

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 (7-8weeks) and adult (12-13weeks) 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, 4.0V, 2.0-ms pulses, 1-16Hz) were measured. In all groups, stimulation of the vagal afferents below 16Hz produced frequency-dependent reductions in RSNA, HR and MAP, while a 16Hz 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 16Hz did not differ between groups; however, area under the curve values were greater in the LPK versus Lewis (overall, 9±1 versus 19±3μVs, 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.