title: Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats.
abstract: Peripheral chemoreflex sensitization is a feature of renovascular hypertension. Carotid sinus nerve denervation (CSD) has recently been shown to relieve hypertension and reduce sympathetic activity in other rat models of hypertension. We show that CSD in renovascular hypertension halts further increases in blood pressure. Possible mechanisms include improvements in baroreceptor reflex sensitivity and renal function, restoration of cardiac calcium signalling towards control levels, and reduced neural inflammation. Our data suggest that the peripheral chemoreflex may be a viable therapeutic target for renovascular hypertension.
  
  
  
  The peripheral chemoreflex is known to be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt hypertensive (two kidney one clip; 2K1C) rats. We have previously shown that carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and reveal the potential underlying mechanisms. Adult Wistar rats were instrumented to record ABP via telemetry, and then underwent CSD (n = 9) or sham CSD (n = 9) 5 weeks after renal artery clipping, in comparison with normal Wistar rats (n = 5). After 21 days, renal function was assessed, and tissue was collected to assess sympathetic postganglionic intracellular calcium transients ([Ca2+]i) and immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in ABP (Wistar: 98 ± 4 mmHg vs. 2K1C: 147 ± 8 mmHg; P < 0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca2+]Iin stellate neurons (P < 0.05). CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14 ± 2 mmHg by week 3 (P < 0.01), which was accompanied by improvements in both baroreflex control and spectral indicators of cardiac sympatho-vagal balance. Furthermore, CSD improved protein and albuminuria, decreased [Ca2+]ievoked responses from stellate neurons, and also reduced indicators of brainstem inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and improves renal function. This may be mediated by improvements in autonomic balance, functional remodelling of post-ganglionic neurons and reduced inflammation. Our results suggest that the peripheral chemoreflex may be considered as a potential therapeutic target for controlling renovascular hypertension.
authors: School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.
authors: Wioletta
authors: W
authors: Pijacka
authors: School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.|Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors: Fiona D
authors: FD
authors: McBryde
authors: Department of Pharmacology and Physiology, The George Washington University School of Medical and Health Sciences, Washington, DC, USA.
authors: Paul J
authors: PJ
authors: Marvar
authors: Cardiovascular Division - Department of Physiology, Escola Paulista de Medicina, Universidade Federal de, Sao Paulo, Brazil.
authors: Gisele S
authors: GS
authors: Lincevicius
authors: School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK.
authors: Ana P L
authors: AP
authors: Abdala
authors: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
authors: Lavinia
authors: L
authors: Woodward
authors: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
authors: Dan
authors: D
authors: Li
authors: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
authors: David J
authors: DJ
authors: Paterson
authors: School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol, UK. julian.f.r.paton@bristol.ac.uk.
authors: Julian F R
authors: JF
authors: Paton
mesh_terms: D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D020013:Calcium Signaling; D002346:Carotid Sinus / Q000294:innervation* / Q000601:surgery; D002478:Cells, Cultured; D006978:Hypertension, Renovascular / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013562:Sympathectomy; D017779:Sympathetic Fibers, Postganglionic / Q000502:physiology / Q000601:surgery
keywords: carotid sinus denervation; chemoreceptor reflex; renovascular hypertension