Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar rats

Author Pijacka, Wioletta Google Scholar
McBryde, Fiona D. Google Scholar
Marvar, Paul J. Google Scholar
Lincevicius, Gisele S. Autor UNIFESP Google Scholar
Abdala, Ana Paula Lima Google Scholar
Woodward, Lavinia Google Scholar
Li, Dan Google Scholar
Paterson, David J. Google Scholar
Paton, Julian F. R. Google Scholar
Abstract 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) 5weeks after renal artery clipping, in comparison with normal Wistar rats (n=5). After 21days, 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: 984mmHg vs. 2K1C: 1478mmHg

P<0.001), coupled with impairments in renal function and baroreflex sensitivity, increased neuroinflammatory markers and enhanced [Ca2+](I) in 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 142mmHg 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+](i) evoked 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.
Keywords carotid sinus denervation
chemoreceptor reflex
renovascular hypertension
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor British Heart Foundation
Royal Society
National Institutes of Health (NIH)
European Commission Research Executive Agency Marie Curie International Incoming Fellowship
American Heart Association
Grant number British Heart Foundation: RG/12/6/29670
NIH: 1R01AT008632-01
NIH: R00 HL107675-03
European Commission Research Executive Agency Marie Curie International Incoming Fellowship: MC-IIF - 276147
American Heart Association: 15CSA24340001
Date 2016
Published in Journal Of Physiology-London. Hoboken, v. 594, n. 21, p. 6255-6266, 2016.
ISSN 0022-3751 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 6255-6266
Origin http://dx.doi.org/10.1113/JP272708
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000387084200016
URI https://repositorio.unifesp.br/handle/11600/56846

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