Reversing gene expression in cardiovascular target organs following chronic depression of the paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in spontaneous hypertensive rats

Vera Geraldes, Nataniel Goncalves-Rosa, Julian F R Paton, Tiago F. Outeiro, Isabel Rocha

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
299 Downloads (Pure)

Abstract

Background
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).

Objective
Evaluate gene expression in end-organs of SHR after a chronic overexpression of hKir2.1 channels in either the PVN or RVLM. Methods 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).

Results
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, Ca2+-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.

Conclusion
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.
Original languageEnglish
Pages (from-to)109-115
Number of pages7
JournalBrain Research
Volume1646
Early online date27 May 2016
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • mRNA
  • Hypertension
  • Sympathetic Nervous System
  • kidney
  • heart
  • common carotid artery

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