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


METHODS
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.


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
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.
Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Maja
M
Lozić
Michael
M
Greenwood
Olivera
O
Šarenac
Andrew
A
Martin
Charles
C
Hindmarch
Tatjana
T
Tasić
Julian
J
Paton
David
D
Murphy
Nina
N
Japundžić-Žigon
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000502:physiology*
D018045:Receptors, Oxytocin