Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication

Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication
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DOI:
10.1038/hr.2015.122
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发表时间:
2016-02-01
影响因子:
5.4
通讯作者:
Plachta, Dennis T. T.
Plachta, Dennis T. T.
中科院分区:
医学2区
文献类型:
--
作者:
Gierthmuehlen, Mortimer;Plachta, Dennis T. T.

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选择性迷走神经刺激(sVNS)已被证明可以降低大鼠的血压,而且没有主要的副作用。这项技术可能成为难治性高血压患者非药物降压治疗的关键。受体阻滞剂是高血压的一线治疗药物,通常具有心动过缓的作用。由于VNS本身也可以促进心动过缓,因此本研究的目的是研究β - 1选择性阻滞剂美托洛尔对sVNS效果的影响,特别是对心率的影响。在10只雄性Wistar大鼠中,在迷走神经束周围放置聚酰亚胺多通道袖带电极,选择性刺激主动脉减压神经纤维。刺激参数根据动物个体阈值调整,频率30 ~ 50 Hz,幅度0.3 ~ 1.8 mA,脉宽0.3 ~ 1.3 ms。用颈动脉内的微尖端传感器检测血压反应,用s.c.胸电极记录心电图。静脉给予美托洛尔(2 mg kg(-1)体重)后,动物平均动脉血压(MAP)和心率(HR)明显降低。虽然选择性电刺激压力感受纤维会降低MAP和HR,但美托洛尔能显著缓解这两种影响。作为副作用,美托洛尔给药后刺激性呼吸暂停的发生率显著增加。sVNS可以降低美托洛尔下的MAP,而不会引起严重的心动过缓。
Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. beta-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the beta 1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.