title: Angiotensin II and angiotensin-(1-7) in paraventricular nucleus modulate cardiac sympathetic afferent reflex in renovascular hypertensive rats.
abstract: BACKGROUND
  The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributes to the pathogenesis and progression of hypertension. Activation of AT(1) receptors by angiotension (Ang) II in the paraventricular nucleus (PVN) augments the enhanced CSAR and sympathetic outflow in hypertension. The present study is designed to determine whether Ang-(1-7) in PVN plays the similar roles as Ang II and the interaction between Ang-(1-7) and Ang II on CSAR in renovascular hypertension.
  
  
  RESULTS
  The two-kidney, one-clip (2K1C) method was used to induce renovascular hypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardial application of capsaicin in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. Either Ang II or Ang-(1-7) in PVN caused greater increases in RSNA and MAP, and enhancement in CSAR in 2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT(1) receptor antagonist losartan induced opposite effects to Ang-(1-7) or Ang II respectively in 2K1C rats, but losartan had no effects in Sham rats. Losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatment with Ang-(1-7) dose-dependently augmented the RSNA, MAP, and CSAR responses to the Ang II in 2K1C rats. Ang II level, AT(1) receptor and Mas receptor protein expression in PVN increased in 2K1C rats compared with Sham rats but Ang-(1-7) level did not.
  
  
  CONCLUSIONS
  Ang-(1-7) in PVN is as effective as Ang II in enhancing the CSAR and increasing sympathetic outflow and both endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension. Ang-(1-7) in PVN potentiates the effects of Ang II in renovascular hypertension.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Chen
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Xiong
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013599:Systole / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan