In a paper by Stojicic et al (2008) we found that central V2 vasopressin antagonist modulates cardiovascular homeostasis. To further asses the role of central vasopressin V2 receptors we performed experiments in adult male Wistar rats overexpressing V2 receptors in hypothalamic paraventricular nucleus, the major integrative site of stress response. Under xylazine/ketamine anesthesia (0.4ml 10% ketamine IP, 0.1ml 2% xylazine IP per animal) TA-11-PA C40 DSI implants were introduced in aorta followed by metamizol treatment (200mg, IP). After ten days rats were exposed to stereotaxic surgery (anaesthetics as above): glass micropipettes containing 1:1 mixture of the replication-deficient adenoviral vectors Ad.CMV.eGFP (titer, 1.57×1010 pfu/ml) plus Ad.CMV.V2 (2.5 x1010pfu/ml) or Ad.CMV.eGFP (control), were injected in PVN (Qiu et al. (2007)). Seven days elapsed before full expression of transfected genes and beginning of the 10 minute air-jet stress protocol. Only animals in which eGFP expression was observed within the PVN were subjects of cardiovascular signal analysis and one-way ANOVA statistical significance evaluation. All experiments were performed in accordance with Directive 86/609/ECC. Systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) were derived from the arterial blood pressure digitalized at 1000Hz, as maximum, minimum and inverse of interbeat interval, respectively. Evaluation of the spontaneous BRR was performed by using the method of sequences and calculation of baroreceptor reflex sensitivity (BRS) and effectiveness index (BEI). Time spectra were created using fast Fourier transform algorithm on 15 overlapping 2048 point time series involving 410-s registration period. Spectra were analyzed in very-low-frequency (VLF:0.0195-0.195Hz), low-frequency (LF:0.195-0.8Hz) and high-frequency (HF:0.8-3Hz) range. Basal values of cardiovascular parameters did not differ between groups. Exposure of rats to air-jet stress increased SBP(137.81±5.36mmHg, p<0.05, and 144.23±5.14mmHg, p<0.05), DBP(107.94±3.36 mmHg, p<0.01 and 107.92±5.85mmHg, p<0.01), HR(447.92±16.59Hz p<0.01 and 465.57 Hz p<0.01), LF SBP(3.97±0.56mmHg2/Hz, p<0.05 and 4.58±0.7256mmHg2/Hz, p<0.05) and HF SBP(1.79±0.36 mmHg2/Hz, p<0.05 and 3.20±1.75 mmHg2/Hz, p<0.001)in both groups of rats. In HR spectra, only transfected rats exhibited significant increase of LH HR(81.59±47.12 mmHg2/Hz, p<0.05) and HF HR(119.5±63.2 mmHg2/Hz, p<0.05) and reduced LF/HF HR ratio. In control rats exposure to air-jet stress reduced BRS, whereas in transfected rats BRS remained close to baseline values. The results indicate that overexpression of V2 receptors in PVN of rats increases vagal control of the heart and preserves the baroreceptor reflex functioning during stress.
University College Dublin (2009) Proc Physiol Soc 15, C5
Oral Communications: Upregulation of vasopressin V2 receptors in paraventricular nucleus of rats modulates cardiovascular response to acute panic
M. Lozic1, O. Sarenac1, J. Paton2, D. Murphy2, N. Japundzic-Zigon1
1. Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, Belgrade, Serbia. 2. Bristol University, Bristol, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.