01whole.pdf (13.73 MB)
Renal sensory nerves play a role in the hypotensive effect of renal denervation in chronic kidney disease
thesisposted on 2022-03-28, 12:45 authored by Sheran Li
Renal denervation is a novel therapy being used to reduce high blood pressure in patients with chronic kidney disease (CKD). We investigated the contribution of renal sensory and sympathetic nerves to this response using a Lewis polycystic kidney (LPK) model of CKD. Lewis control and LPK rats were subjected to total, afferent or sham renal denervation by periaxonal application of phenol, capsaicin or normal saline, respectively, at age 6 and 12 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography or radiotelemetry. Renal function was assessed by urinalysis and creatinine clearance rate. Denervation was confirmed by immunohistochemistry using antibodies against markers for sensory [calcitonin gene-related peptide [(CGRP)] and sympathetic nerves [tyrosine hydroxylase (TH)] in the kidney. Initial analysis indicates total denervation produces a blood-pressure lowering effect in LPK between age 7-15 weeks (treat 164±4 vs. sham 180±6mmHg as determined by tail-cuff, P=0.003). SBP in LPK between age 7-11 weeks was also lesser in the afferent denervation group (treated 205±16 vs. sham 222±13mmHg, as determined by radiotelemetry, P<0.05). Neither denervation technique altered SBP in the Lewis animals. Neither total nor afferent denervation had an effect on renal function. In both strains of rat, 4 weeks following the second denervation surgery, TH labelling remained intact after afferent denervation, but was markedly reduced after total denervation. CGRP labelling was markedly reduced after both total and afferent denervation when compared to sham animals. This preliminary study provides evidence supporting the hypothesis that renal sensory nerves have an important role in the observed hypotensive effect of renal denervation.