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Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats
Author(s) -
Lozić Maja,
Greenwood Michael,
Šarenac Olivera,
Martin Andrew,
Hindmarch Charles,
Tasić Tatjana,
Paton Julian,
Murphy David,
JapundžićŽigon Nina
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12776
Subject(s) - baroreceptor , oxytocin , receptor , endocrinology , medicine , hypothalamus , baroreflex , oxytocin receptor , vasopressin , reflex , chemistry , blood pressure , heart rate
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 ( A d), engineered to overexpress OT receptors, and an enhanced green fluorescent protein ( eGFP ) tag. Control groups: PVN was transfected with an A d expressing eGFP alone or untransfected, sham rats ( W t). 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.