Over-expression of V1a receptors in PVN modulates autonomic cardiovascular control

Maja Lozić, Tatjana Tasić, Andrew Martin, Michael Greenwood, Olivera Šarenac, Charles Hindmarch, Julian F. Paton, David Murphy, Nina Japundžić-Žigon

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

7 Citations (Scopus)
278 Downloads (Pure)

Abstract

The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress. Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress. However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology.
Original languageEnglish
Pages (from-to)185-195
Number of pages11
JournalPharmacological Research
Volume114
Early online date31 Oct 2016
DOIs
Publication statusPublished - Dec 2016

Keywords

  • Vasopressin
  • V1a receptor
  • Paraventricular nucleus
  • Adenoviral vector
  • Baroreflex
  • Blood pressure variability
  • Heart rate variability

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