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

Hypertens Res. 2016 Feb;39(2):79-87. doi: 10.1038/hr.2015.122. Epub 2015 Nov 19.


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. β-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 β1-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Arterial Pressure / drug effects
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology*
  • Carotid Arteries / drug effects
  • Carotid Arteries / physiology
  • Electrocardiography / drug effects
  • Heart Rate / drug effects*
  • Heart Rate / physiology*
  • Male
  • Metoprolol / pharmacology*
  • Pressoreceptors / drug effects
  • Rats
  • Rats, Wistar
  • Respiratory Rate / drug effects*
  • Respiratory Rate / physiology*
  • Vagus Nerve Stimulation / methods*


  • Adrenergic beta-1 Receptor Antagonists
  • Antihypertensive Agents
  • Metoprolol