Transcriptome Analysis Reveals Downregulation of Urocortin Expression in the Hypothalamo-Neurohypophysial System of Spontaneously Hypertensive Rats

Andrew Martin, Andre S Mecawi, Vagner R Antunes, Song T Yao, Jose Antunes-Rodrigues, Julian F R Paton, Alex Paterson, Michael Greenwood, Olivera Šarenac, Bojana Savić, Nina Japundžić-Žigon, David Murphy*, Charles C T Hindmarch*

*Corresponding author for this work

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

Abstract

The chronically increased blood pressure characteristic of essential hypertension represents an insidious and cumulative risk for cardiovascular disease. Essential hypertension is a multifactorial condition, with no known specific aetiology but a strong genetic component. The Spontaneously Hypertensive rat (SHR) shares many characteristics of human essential hypertension, and as such is a commonly used experimental model. The mammalian hypothalamo-neurohypophyseal system (HNS) plays a pivotal role in the regulation of blood pressure, volume and osmolality. In order to better understand the possible role of the HNS in hypertension, we have used microarray analysis to reveal differential regulation of genes in the HNS of the SHR compared to a control normotensive strain, the Wistar Kyoto rat (WKY). These results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). One of the genes identified and validated as being downregulated in SHR compared to WKY was that encoding the neuropeptide urocortin (Ucn). Immunohistochemical analyses revealed Ucn to be highly expressed within magnocellular neurons of the PVN and SON, with pronounced localisation in dendritic projections containing oxytocin and vasopressin. When Ucn was overexpressed in the PVN of the SHR by in vivo lentiviral mediated gene transfer, blood pressure was unaffected but there were significant, transient reductions in the VLF spectra of systolic blood pressure consistent with an action on autonomic balance. We suggest that Ucn may act, possibly via dendritic release, to subtly regulate neurohumoral aspects of arterial pressure control.
Original languageEnglish
Article number599507
Number of pages18
JournalFrontiers in Physiology
Volume11
DOIs
Publication statusPublished - 17 Mar 2021

Bibliographical note

Funding Information:
We acknowledge the generous financial support of the BHF (FS/12/5/29339, AM and DM; RG/11/28714, DM and JP) and the BBSRC (BB/J005452/1, DM, JP, CH, and VRA; BB/J015415/1, DM, JP, JA-R, and OŠ). SY was supported by an Australian Research Council Future Fellowship (FT170100363). VRA is Brazilian Research Council Fellow (CNPq): # 304970/2017-4.

Publisher Copyright:
© Copyright © 2021 Martin, Mecawi, Antunes, Yao, Antunes-Rodrigues, Paton, Paterson, Greenwood, Šarenac, Savić, Japundžić-Žigon, Murphy and Hindmarch.

Keywords

  • hypothalamo-neurohypophyseal system
  • transcriptome
  • SHR
  • UCN
  • spectral analysis
  • microarray
  • hypertension

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