Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control.
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.
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia.
Maja
M
Lozić
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia.
Tatjana
T
Tasić
Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, England BS1 3NY, United Kingdom.
Andrew
A
Martin
Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, England BS1 3NY, United Kingdom.
Michael
M
Greenwood
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia; Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, England BS1 3NY, United Kingdom.
Olivera
O
Šarenac
Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, England BS1 3NY, United Kingdom; Department of Physiology, University of Malaya, University of Malaya, Kuala Lumpur 50603, Malaysia.
Charles
C
Hindmarch
School of Physiology and Pharmacology, University of Bristol, Bristol, England BS8 1TD, United Kingdom.
Julian F
JF
Paton
Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, England BS1 3NY, United Kingdom; Department of Physiology, University of Malaya, University of Malaya, Kuala Lumpur 50603, Malaysia.
David
D
Murphy
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Belgrade, 11000 Belgrade, Serbia. Electronic address: nzigon@med.bg.ac.rs.
Nina
N
Japundžić-Žigon
D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D006339:Heart Rate; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D015854:Up-Regulation
D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat
Adenoviral vector; Baroreflex; Blood pressure variability; Heart rate variability; Paraventricular nucleus; V1a receptor; Vasopressin