Surprising Ways the Vagus Nerve Activates During Exercise

In 1921, Otto Loewi (1873-1961) conducted experiments in frogs that used electrical stimulation to activate the vagus nerve. He discovered that stimulating the vagus nerve triggered the release of a parasympathetic substance that slowed heart rate and calmed the nervous system.

Loewi, a German-born pharmacologist and physician, won a Nobel Prize for this discovery. Over 100 years ago, Loewi named this newly discovered vagus nerve neurotransmitter "vagusstoff" (German: vagus stuff). Today, vagusstoff is called acetylcholine.

For the past century, vagus nerve stimulation (VNS) and increased vagal nerve activity have been associated with our parasympathetic nervous system's calming, "rest and digest" capacity. (See "How Does Vagusstoff Calm Us Down?")

Conversely, when the sympathetic nervous system's "fight or flight" stress response is triggered, most experts have long believed that vagal nerve activity automatically decreases.

Along these lines, until very recently, it was widely believed that during cardio workouts (like jogging on a treadmill), vagal nerve activity decreased because running is a "fight or flight" (not "rest and digest") type of activity.

New Study: Cardio Increases Vagus Nerve Activity

Schematic representation of the cardiac effect of increased vagal activity during exercise mediated by acetylcholine and vasoactive intestinal peptide (VIP).

Source: Shanks et al. (2023) Circulation Research/Creative Commons (CC BY-NC)

A new study in sheep—who trotted on a treadmill for 18 minutes at a stretch while their vagus nerve activity was monitored—rocks the boat and turns what we thought we knew about how the vagus nerve responds to exercise on its head.

The latest study of exercising sheep by researchers at New Zealand's University of Auckland suggests that cardiorespiratory exercise increases cardiac vagal nerve activity, which enhances coronary blood flow to the heart. These findings (Shanks et al., 2023) were recently published in the open-access, peer-reviewed journal Circulation Research.

"Our study finds the activity in these 'rest and digest' vagal nerves actually increases during exercise," senior author Rohit Ramchandra said in a September 2023 news release.

"For the heart to sustain a high level of pumping, it needs a greater blood flow during exercise to fuel the increased work it is doing: our data indicate that the increase in vagal activity does just this," he added.

For this study, Ramchandra's research group, led by first author Julia Shanks, used "tour de force" electrical recording techniques to monitor how the vagus nerve functioned while sheep were exercising. In a finding that disrupts the status quo, this study suggests that cardiac vagal nerve activity increases during exercise to enhance the heart's coronary blood flow.

During Exercise, the Vagus Nerve Releases Vasoactive Intestinal Peptide (VIP)

Notably, the researchers found that the vagus nerve releases vasoactive intestinal peptide (VIP) during exercise. VIP stimulates contractility, which allows the heart to contract more vigorously. It also causes vasodilation, which widens arteries and increases the heart's blood supply.

As mentioned, until recently, most vagal nerve research has focused on a calming, "rest and digest" parasympathetic neurotransmitter called acetylcholine, first discovered by Otto Loewi in 1921.

"The cardiac vagus nerve releases multiple mediators. Previous research has focused on [the] neurotransmitter acetylcholine," Ramchandra explains. "Our study focused on a different mediator, vasoactive intestinal peptide (VIP). [We found] that the vagus nerve releases this peptide during exercise, which helps the coronary vessels dilate, allowing more blood to pump through the heart."

This study shows for the first time that when a large mammal (sheep) does aerobic exercise on a treadmill, the vagus nerve releases VIP, which mediates the increase of coronary blood flow to the heart observed during cardiorespiratory activity.

"Vasoactive intestinal peptide was first found in the gut. [VIP] does help digestion, but we now know it is also important in exercise," Shanks said in the news release. According to this study, when the vagus nerve releases VIP during cardio, it enhances coronary blood flow, strengthens heart contractions, and improves a large mammal's "fight or flight" capacities.

Human Research Is Needed to Confirm These Animal Study Findings

To the best of my knowledge, the latest (2023) cardiac vagal nerve activity study by University of Auckland researchers is the first to show that doing aerobic exercise on a treadmill can stimulate the vagus nerve and enhance coronary artery blood flow. That said, this animal research was conducted in exercising sheep (not people) who trotted on a treadmill for 18 minutes per "workout" while their vagus nerve activity was monitored.

Vagus Nerve Essential Reads

Does Vagus Nerve Activity Make Jogging More Enjoyable?

5 Ways to Care for the Most Important Nerve In Your Body

Although sheep are large mammals that share many neurobiological similarities with Homo sapiens, human studies are needed to see if aerobic exercise increases cardiac vagal nerve activity and enhances coronary blood flow in people the same as in sheep.