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

Frontiers in Physiology

Andrew Martin¹  David Murphy¹  Michael Greenwood¹  Alex Paterson¹  Vagner R. Antunes²  Jose Antunes-Rodrigues³  Olivera Šarenac⁴  Nina Japundžić-Žigon⁴  Bojana Savić⁴  Song T. Yao⁵  Andre S. Mecawi⁶  Julian F. R. Paton⁷  Charles C. T. Hindmarch⁸ 

[1] Bristol Medical School: Translational Health Sciences, Dorothy Hodgkin Building, University of Bristol, Bristol, United Kingdom;Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil;Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade, Belgrade, Serbia;Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia;Laboratory of Neuroendocrinology, Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil;Manaaki Mānawa, The Heart Research Centre, University of Auckland, Auckland, New Zealand;Queen’s Cardiopulmonary Unit, Department of Medicine, Translational Institute of Medicine, Queen’s University, Kingston, ON, Canada;

关键词: hypothalamo-neurohypophyseal system;    transcriptome;    SHR;    UCN;    spectral analysis;    microarray;   

DOI  :  10.3389/fphys.2020.599507

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown