title: 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.
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: ibraheem_muhammed@yahoo.com.
authors: Ibrahim M
authors: IM
authors: Salman
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
authors: Cara M
authors: CM
authors: Hildreth
authors: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
authors: Jacqueline K
authors: JK
authors: Phillips
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000502:physiology; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology*; D008297:Male; D011917:Rats, Inbred Lew; D012018:Reflex / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014630:Vagus Nerve / Q000503:physiopathology*
keywords: Cardiac vagal outflow; Chronic kidney disease; Hypertension; Renal sympathetic nerve activity; Vagal afferents