Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep.
Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed.
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.). lindsea.booth@florey.edu.au.
Lindsea C
LC
Booth
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Erika E
EE
Nishi
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Song T
ST
Yao
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Rohit
R
Ramchandra
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Gavin W
GW
Lambert
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Markus P
MP
Schlaich
From the Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia (L.C.B., S.T.Y., R.R., C.N.M.); Baker IDI Heart and Diabetes Institute, Central Clinical School Monash University, Melbourne, Victoria, Australia (M.P.S., G.W.L.); and Department of Physiology, Cardiovascular Division, Federal University of São Paulo, São Paulo, Brazil (E.E.N.).
Clive N
CN
May
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D019771:Axotomy; D001794:Blood Pressure / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology; D017115:Catheter Ablation; D004525:Efferent Pathways / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology / Q000601:surgery; D007668:Kidney / Q000294:innervation*; D009416:Nerve Regeneration / Q000502:physiology*; D009475:Neurons, Afferent / Q000737:chemistry; D009476:Neurons, Efferent / Q000201:enzymology; D009638:Norepinephrine / Q000032:analysis; D011184:Postoperative Period; D012756:Sheep; D013153:Splanchnic Nerves / Q000293:injuries / Q000502:physiology*; D013562:Sympathectomy / Q000379:methods*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D009638:Norepinephrine
cardiovascular diseases; catheter ablation; electric stimulation