Emotional stress may contribute to the development of hypertension. However, the central mechanisms involved in the mediation of the cardiovascular response to emotional stress have not been fully investigated [1]. With the latest discovery of a new vasopressin V1b antagonist with potent anxiolytic activity [2], we were prompted to investigate the contribution of central vasopressin mechanisms in the cardiovascular response to emotional stress. Experiments were performed in conscious rats equipped with left lateral intracerebroventricular (icv) cannula (under 0.4 ml, 10% ketamine plus 0.1 ml, 2% xylazine, i.p. anesthesia) for drug injection and left femoral arterial catheter (under 4% concentration percentage for induction and 2% for maintenance of halothane anesthesia) for arterial pressure recording. Equidistant sampling allowed direct spectral analysis (fast Fourier transform) of SBP and HR in very low (VLF: 0-0.2Hz), low (LF: 0.2-0.8Hz) and high frequency (HF: 0.8-3Hz) domains. Rats were submitted to two models of stress: air-jet (by blowing air into the nose of a rat for 2 min, n=6) and immobilization (by covering rat with Plexiglas restrainer for 15 min, n=6). Air-jet induced a sharp rise in SBP (168±3mmHg, p<0.01) and HR (525±10bpm, p<0.01) and gradual recovery with appearance of sympathetically mediated LF BP variability. V1a (SR49059, 100ng, 500ng, icv) and V1b (SSR149415, 100ng, 500ng, icv) antagonists (n=6/each group) did not modify basal values but did reduce the increase of the area under the SBP curve (sum of SBP values, 3.6×105±0.1mmHg, p<0.05 in nontreated rats, 3.3×105±0.2mmHg, p>0.05 in 100ng V1a PT rats, 3.4×105±0.2mmHg, p>0.05 in 500ng V1a PT rats, 3.2×105±0.2mmHg, p>0.05 in 100ng V1b PT rats and 3.3×105±0.1mmHg, p>0.05 in 500ng V1b PT rats), the increase of HRmax (488±10bpm, p<0.05 and 469±14bpm, p<0.05, respectively) during exposure to air-jet and shortened the recovery period of SBP (361±22s in nontreated rats, 206±46s, p<0.001 in 100ng V1a PT rats, 113±15s, p<0.001 in 500ng V1a PT rats, 138±42s, p<0.001 in 100ng V1b PT rats, and 60±8s, p<0.001 in 500ng V1b PT rats) and HR (378±18s in nontreated rats, 216±43s, p<0.05 in 100ng V1a PT rats, 138±21s, p<0.001 in 500ng V1a PT rats, 175±57s, p<0.001 in 100ng V1b PT rats and 140±26s, p<0.001 in 500ng V1b PT rats) and prevented the appearance of LF-SBP. The V1b also reduced the SBPmax increase during exposure to stress (145±9mmHg, p<0.05 in 100ng V1b PT rats and 151±5mmHg, p<0.05 in 500ng V1b PT rats). Immobilization induced a rise of SBP (153±4mmHg, p<0.01), LF-SBP and respiratory-related HF-SBP variability; it did not affect HR but did enhance the vagally mediated HF-HR variability. Both V1a and V1b (n=6/each group) reduced the evoked increases in SBP and SBP variability during immobilization. The V1a PT rats submitted to immobilization now exhibited significant tachycardia (495±65bpm, p<0.05) and failed to increase HF-HR variability. The results suggest that both vasopressin V1a and V1b receptors are involved in the central mediation of the cardiovascular response of rats exposed to emotional stress.
University of Bristol (2007) Proc Physiol Soc 5, C4
Oral Communications: Central vasopressin mechanisms contribute to the mediation of the cardiovascular response to stress
Nina Japundzic-Zigon1, Sonja Stojičić2, Sanja Milutinović1, Olivera Šarenac1, Snezana Milosavljević1, Julian FR Paton3, David Murphy4
1. Pharmacology, School of Medicine University of Belgrade, Belgrade, Serbia, Yugoslavia. 2. Conservative Dentistry and Endodontics, School of Dentistry, Belgrade, Serbia, Yugoslavia. 3. Physiology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, England, United Kingdom. 4. The Molecular Neuroendocrinology Research Group, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, England, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.