Oikawa Ryo, Nasa Yoshihisa, Ishii Rie, Kuwaki Tomoyuki, Tanoue Akito, Tsujimoto Gozoh, Takeo Satoshi
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo, Japan.
Eur J Pharmacol. 2007 Mar 8;558(1-3):144-50. doi: 10.1016/j.ejphar.2006.11.063. Epub 2006 Dec 12.
The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts its physiological actions via 3 distinct receptor isoforms designated V1A, V1B, and V2. We recently showed that V1A receptor was involved in the baroreflex control of heart rate using V1A receptor knockout mice. The present study was undertaken to further clarify this finding. In conscious mice, resting blood pressure of the knockout group was lower than that of the wild-type group (wild-type, 108+/-2.0 mm Hg; knockout, 98+/-3.8 mm Hg; n=6-7) without notable change in heart rate. Although phenylephrine and nitroprusside-induced changes in blood pressure did not differ in these strains, the subsequent bradycardia and tachycardia were markedly blunted in the knockout mice (mean slopes for baroreflex curve after phenylephrine treatment; wild-type, -5.65+/-0.30 bpm/mm Hg; knockout, -3.97+/-0.52 bpm/mm Hg; those after nitroprusside treatment; wild-type, -0.51+/-0.10 bpm/mm Hg; knockout, -0.18+/-0.05 bpm/mm Hg; n=6-7). Under urethane anesthesia (1.0-1.2 g/kg, i.p.), electrical stimulation of the vagal afferent nerve evoked frequency-dependent hypotension and bradycardia in the wild-type mice. In contrast, in the knockout mice such stimulation induced a pressor, not a depressor, response and diminished bradycardia. Moreover, electrical stimulation-induced hemodynamic changes through the vagal afferent nerve in the wild-type mice were significantly attenuated by pretreatment with intravenously administered V1A receptor antagonist d(CH(2))(5)Tyr(Me)AVP. Electrical stimulation of the vagal efferent nerve-induced hemodynamic changes (depressor and bradycardia) and chronotropic responses to adrenergic and cholinergic stimuli were not different between the 2 strains. These results suggest that the V1A receptor in the central nervous system is involved in the regulation of the heart rate via the baroreflex arc.
神经垂体肽[精氨酸（8）] - 血管加压素（AVP）通过3种不同的受体亚型发挥其生理作用，分别命名为V1A、V1B和V2。我们最近使用V1A受体基因敲除小鼠表明V1A受体参与心率的压力反射控制。本研究旨在进一步阐明这一发现。在清醒小鼠中，基因敲除组的静息血压低于野生型组（野生型，108±2.0 mmHg；基因敲除型，98±3.8 mmHg；n = 6 - 7），心率无明显变化。尽管去氧肾上腺素和硝普钠引起的血压变化在这些品系中没有差异，但基因敲除小鼠随后的心动过缓和心动过速明显减弱（去氧肾上腺素治疗后压力反射曲线的平均斜率；野生型，-5.65±0.30次/分钟/mmHg；基因敲除型，-3.97±0.52次/分钟/mmHg；硝普钠治疗后；野生型，-0.51±0.10次/分钟/mmHg；基因敲除型，-0.18±0.05次/分钟/mmHg；n = 6 - 7）。在氨基甲酸乙酯麻醉（1.0 - 1.2 g/kg，腹腔注射）下，电刺激迷走神经传入神经在野生型小鼠中诱发频率依赖性低血压和心动过缓。相反，在基因敲除小鼠中，这种刺激诱发升压反应而非降压反应，并减弱心动过缓。此外，静脉注射V1A受体拮抗剂d（CH2）5Tyr（Me）AVP预处理可显著减弱野生型小鼠中电刺激通过迷走神经传入神经引起的血流动力学变化。电刺激迷走神经传出神经引起的血流动力学变化（降压和心动过缓）以及对肾上腺素能和胆碱能刺激的变时反应在两个品系之间没有差异。这些结果表明，中枢神经系统中的V1A受体通过压力反射弧参与心率调节。
