Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats

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

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

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Abstract

BACKGROUND AND PURPOSE: The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis.

EXPERIMENTAL APPROACH: Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively.

KEY RESULTS: Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress.

CONCLUSIONS AND IMPLICATIONS: OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.

Original languageEnglish
Pages (from-to)4385-4398
Number of pages14
JournalBritish Journal of Pharmacology
Volume171
Issue number19
Early online date5 Sep 2014
DOIs
Publication statusPublished - Oct 2014

Bibliographical note

© 2014 The British Pharmacological Society.

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