title: Reversing gene expression in cardiovascular target organs following chronic depression of the paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in spontaneous hypertensive rats.
abstract: Chronic overexpression of an inwardly rectifying potassium channel (hKir2.1) in the paraventricular nucleus of the hypothalamus (PVN) and in the rostral ventrolateral medulla (RVLM) to suppress neuronal excitability, resulted in a long term decrease of blood pressure and sympathetic output in spontaneously hypertensive rats (SHR).
  
  
  
  Evaluate gene expression in end-organs of SHR after a chronic overexpression of hKir2.1 channels in either the PVN or RVLM.
  
  
  
  mRNA levels of 16 genes known to be involved with blood pressure regulation were evaluated using RT-PCR in tissues from the heart, common carotid artery and kidney of SHR submitted to chronic depression of PVN and RVLM excitability using a lentiviral vector (LVhKir2.1).
  
  
  
  In SHR hearts in which either the PVN or RVLM were injected with LVhKir2.1, there was a downregulation of angiotensin II receptor 1b (AT1), ATPase, Ca(2+)-transporter, troponin T2 and tropomyosin2 (only in RVLM) relative to the sham group. In the kidney of SHR with LVhKir2.1 injections in PVN and RVLM, angiotensinogen, angiotensin II receptor2 (AT2) and endothelin1 were all upregulated compared to sham. In the carotid artery, endothelin2, endothelin receptor A and B were up-regulated following LVhKir2.1 in to either the PVN or RVLM relative to sham.
  
  
  
  Chronic overexpression of hKir2.1 channels in PVN and RVLM, promoted a BP decrease with up-regulation of angiotensinogen and AT2 genes expression in the kidney and down-regulation of AT1 in the heart of SHR. Thus, we demonstrate the potential efficacy of central manipulation to protect against end-organ damage in essential hypertension.
authors.affiliation: Institute of Physiology, Faculty of Medicine and Cardiovascular Centre of University of Lisbon, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Geraldes
authors.affiliation: Institute of Physiology, Faculty of Medicine and Cardiovascular Centre of University of Lisbon, Portugal.
authors.forename: Nataniel
authors.initials: N
authors.lastname: Goncalves-Rosa
authors.affiliation: Institute of Physiology, Faculty of Medicine and Cardiovascular Centre of University of Lisbon, Portugal.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Tavares
authors.affiliation: School of Physiology & Pharmacology, Biomedical Sciences, University of Bristol, Bristol, UK.
authors.forename: Julian F R
authors.initials: JFR
authors.lastname: Paton
authors.affiliation: Institute of Physiology, Faculty of Medicine and Cardiovascular Centre of University of Lisbon, Portugal. Electronic address: isabelrocha0@gmail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001794:Blood Pressure; D017536:Carotid Artery, Common / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors; D007668:Kidney / Q000378:metabolism*; D016086:Lentivirus / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger
keywords: Common carotid artery; Heart; Hypertension; Kidney; Sympathetic nervous system; mRNA