title: Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats.
abstract: BACKGROUND
  Impairment of arterial baroreflex sensitivity is associated with mortality in patients with chronic heart failure (CHF). Elevation of plasma angiotension II (Ang II) contributes to arterial baroreflex dysfunction in CHF. A reduced number of voltage-gated sodium (Nav) channels in aortic baroreceptor neurons are involved in CHF-blunted arterial baroreflex.
  
  
  METHODS
  In this study, we investigated acute effect of Ang II on Nav currents in the aortic baroreceptor neuron and on arterial baroreflex in sham and coronary artery ligation-induced CHF rats.
  
  
  RESULTS
  Using Ang II I radioimmunoassay, real-time reverse transcription-PCR and western blot, we found that Ang II levels, and mRNA and protein expression of angiotension II type 1 receptor in nodose ganglia from CHF rats were higher than that from sham rats. Local microinjection of Ang II (0.2  nmol) into the nodose ganglia decreased the arterial baroreflex sensitivity in sham rats, whereas losartan (1  nmol, an angiotension II type 1 receptor antagonist) improved the arterial baroreflex sensitivity in CHF rats. Data from patch-clamp recording showed that Ang II (100  nmol/l) acutely inhibited Nav currents in the aortic baroreceptor neurons from sham and CHF rats. In particular, inhibitory effect of Ang II on Nav currents in the aortic baroreceptor neurons was larger in CHF rats than that in sham rats. Losartan (1  μmol/l) totally abolished the inhibitory effect of Ang II on Nav currents in sham and CHF aortic baroreceptor neurons.
  
  
  CONCLUSIONS
  These results suggest that elevation of endogenous Ang II in the nodose ganglia contributes to impairment of the arterial baroreflex function in CHF rats through inhibiting Nav channels.
authors.affiliation: aDepartment of Emergency Medicine bDepartment of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA *Dr Dongze Zhang and Dr Jinxu Liu contributed equally to the writing of this article.
authors.forename: Dongze
authors.initials: D
authors.lastname: Zhang
authors.forename: Jinxu
authors.initials: J
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Huiyin
authors.initials: H
authors.lastname: Tu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Muelleman
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001158:Arteries / Q000503:physiopathology; D017704:Baroreflex / Q000502:physiology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009620:Nodose Ganglion / Q000378:metabolism / Q000503:physiopathology; D011311:Pressoreceptors / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000502:physiology*
chemical_list: D061566:Voltage-Gated Sodium Channels; D000804:Angiotensin II; D012964:Sodium; D019808:Losartan
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