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依那普利给药下大鼠选择性迷走神经刺激的血流动力学反应

Haemodynamic Responses to Selective Vagal Nerve Stimulation under Enalapril Medication in Rats.

作者信息

Gierthmuehlen Mortimer, Stieglitz Thomas, Zentner Josef, Plachta Dennis T T

机构信息

Department of Neurosurgery, University Medical Center Freiburg, Freiburg, Germany.

Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, University of Freiburg, Freiburg, Germany.

出版信息

PLoS One. 2016 Jan 14;11(1):e0147045. doi: 10.1371/journal.pone.0147045. eCollection 2016.

Abstract

Selective vagal nerve stimulation (sVNS) has been demonstrated to lower blood pressure (BP) in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs) are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight), the animals' mean arterial blood pressures (MAPs) decreased significantly, while the heart rates (HRs) were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.

摘要

选择性迷走神经刺激(sVNS)已被证明可降低大鼠血压(BP),且不会引起重大副作用。这种方法可能适用于治疗难治性高血压患者。血管紧张素转换酶抑制剂(CEIs)是首批用于治疗动脉高血压的药物之一,主要通过与肾脏的肾素-血管紧张素系统相互作用来显著降低血压。除了降低血压外,CEI对心肌梗死后的生存率有积极影响;它们可降低中风发生率,并改善心力衰竭患者的神经激素状态。如果sVNS可能作为一种抗难治性高血压的疗法被引入,患者至少会部分继续服用他们的CEI药物。因此,本研究的目的是调查CEI依那普利对sVNS的血流动力学和呼吸效应的影响。在10只雄性Wistar大鼠中,将基于聚酰亚胺的多通道袖带电极放置在迷走神经束周围,以选择性刺激主动脉减压神经纤维。刺激参数根据个体动物的阈值进行调整,包括30至50Hz的重复频率、0.5至1.5mA的幅度以及0.4ms至1.0ms的脉冲宽度。用左颈动脉中的微尖端换能器检测血压反应,并用皮下电极记录心电图。静脉注射依那普利(2mg/kg体重)后,动物的平均动脉血压(MAPs)显著下降,而心率(HRs)未受到显著影响。依那普利减弱了sVNS对血压和心率的影响,但影响仍然存在。我们得出结论,在依那普利治疗期间,sVNS可降低MAP,且无相关副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/4713053/191342e8c919/pone.0147045.g001.jpg

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