Trait: Adrenaline Baseline Level
Dr Haran Sivapalan
December 23, 2019
What is adrenaline?
You’ve probably heard of adrenaline before. A scary movie, loud music and intense exercise are all often described as “getting the adrenaline pumping”.
Adrenaline (also called epinephrine) is the body’s “fight-or-flight” hormone. It prepares us to encounter (‘fight’) or escape (‘flight’) a threatening situation. Accordingly, adrenaline dilates our airways, increases our heart rate, elevates blood glucose levels and diverts blood to skeletal muscle, all of which allow us to react quickly to a perceived threat.
While predominantly functioning as a hormone (i.e. a chemical message transported in the bloodstream) that acts on multiple organs, adrenaline is also a neurotransmitter. Neurotransmitters are chemicals released by nerve endings, which transmit nerve impulses from one nerve to another across a synapse.
Adrenaline is similar in chemical structure to two other important neurotransmitters, dopamine and noradrenaline (norepinephrine). Collectively, adrenaline, dopamine and noradrenaline are known as catecholamines.
- Adrenaline is the body's 'fight-or-flight' hormone.
- Adrenaline primes the body to respond rapidly to a threat.
- Adrenaline is primarily a hormone that circulates in the bloodstream.
- Adrenaline also acts as a neurotransmitter at synapses between nerves.
- Adrenaline belongs to a group of substances known as catecholamines (along with dopamine and noradrenaline).
What are the effects of adrenaline in the body?
The main purpose of adrenaline is to prime us to fight or escape a perceived threat (the so-called ‘fight-or-flight’ or acute stress response). As described below, the effects of adrenaline in the body reflect this purpose.
- Increased heart rate, blood pressure, and blood flow to muscles
Suppose we encountered a threatening situation, say a dangerous animal. We may need to fend off the animal or to suddenly run away. In both these scenarios, our skeletal muscles would require a rapidly increased supply of oxygen and nutrients in blood to fuel muscle contraction. In this respect, adrenaline increases our heart rate, which means more blood is pumped per second to our working muscles.
Similarly, adrenaline causes blood vessels that supply skeletal muscles to dilate (a process called vasodilatation). This increases blood flow to meet the raised energy demands of working muscles.
In concert with this, blood flow is diverted away from tissues that are less urgently required in a threatening situation. For example, when we encounter a dangerous animal, we don’t want to waste energy on digesting food. In this sense, adrenaline reduces blood flow to organs such as the gut, skin and kidneys by narrowing the blood vessels supplying them (a process called vasoconstriction).
Partly as a result of increased heart rate and vasoconstriction, adrenaline also causes a temporary rise in blood pressure. This ensures there is an adequate pressure gradient for blood to flow down to supply muscles, the brain and other organs.
For more on blood pressure, heart rate and blood flow, check out the Nitric Oxide and Blood Flow article.
- Dilation of airways
One of the key substances transported in the blood is oxygen. When faced with a threatening situation, tissues such our brain and skeletal muscles require more oxygen. This is then used to yield chemical energy from glucose through a series of reactions that we call aerobic respiration. In turn, this energy can fuel muscle contraction or nerve activity in our brain.
As well as increasing blood flow to the lungs, adrenaline causes the dilation of our large and small airways(bronchi and bronchioles, respectively). This is known as bronchodilation and it allows a greater amount of air to flow into our lungs and diffuse into blood capillaries. As a result, the level of oxygen in our blood increases and can be used to supply respiring tissues.
- Increase in blood glucose
It isn’t just our muscles that require more energy during a threatening situation. In the scenario with a dangerous animal, we would need to remain extremely vigilant and keep our wits about us. This means our brain would have increased energy demands.
To provide this energy, levels of glucose in the bloodstream must be kept adequately high. Adrenaline achieves this in two ways:
Firstly, it stimulates the liver and skeletal muscle to break down glycogen (an energy storage molecule) into glucose, which is then released in the bloodstream. This process is known as glycogenolysis.
Secondly, adrenaline inhibits the synthesis of new glycogen from glucose (a process called glycogenesis).
- Increase in muscle strength
Some studies show that adrenaline released as part of our ‘fight-or-flight’ response enables fast-twitch muscle fibers to contract with greater force. In biological terms, we describe adrenaline as having a positive inotropic effect.
- Pupil dilation
One well-known effect of adrenaline is to dilate our pupils, thereby letting more light into our eyes. This may allow us to be more vigilant of threats.
- The effects of adrenaline help us react to physical and psychological stressors.
- Adrenaline increases heart rate and blood pressure.
- Adrenaline increases blood flow to exercising muscles.
- Adrenaline decreases blood flow to the gastrointenstinal tract, skin and kidneys.
- Adrenaline dilates our airways, allowing increased blood oxygenation.
- Adrenaline elevates blood sugar levels by promoting the breakdown of glycogen.
What is the role of adrenaline in exercise?
Physical exercise is considered by the body to be a stressor. Accordingly, we activate our ‘fight-or-flight’ response and release adrenaline during exercise.
Many of the effects of adrenaline (described above) are clearly beneficial during exercise. For example, increased heart rate, blood pressure and vasodilatation of local blood vessels allow greater blood flow to exercising muscles. Dilation of airways means we get enough oxygen to sustain aerobic exercise.
Similarly, the breakdown of glycogen by the liver ensures muscles have a steady supply of glucose to fuel muscle contraction.
- Exercise and adrenaline levels
Studies show that levels of adrenaline in blood plasma rise from baseline in response to both dynamic and static exercises. These rises in adrenaline vary according to the duration and intensity of exercise, with exercise intensity having a particularly pronounced effect. Generally speaking, the longer or more intense your workout, the greater the rise in blood adrenaline levels.
Your training status also affects your adrenaline response to exercise. Compared to untrained individuals, trained athletes show far greater increases in blood adrenaline levels during exercise. This is thought to allow trained athletes to respond to higher exercise intensities.
Following exercise, adrenaline levels quickly return to baseline. It remains a topic of debate, but some research suggests that trained athletes have higher baseline (or resting) levels of adrenaline as part of a long-term adaptation to training.
- Adrenaline levels in the blood rise during exercise.
- Adrenaline is beneficial during exercise as it helps our skeletal muscles cope with increased energy demands.
- More intense exercise results in greater increases in blood adrenaline levels.
- Blood adrenaline levels return to baseline after exercise.
Where is adrenaline produced?
Adrenaline is produced by the adrenal glands.
Your adrenal glands sit just above each kidney and are responsible for producing several hormones, including glucocorticoid hormones (such as cortisol), mineralocorticoid hormones (such as aldosterone) and sex steroids (such as testosterone and estrogen).
More specifically, adrenaline is produced from the innermost layer of the adrenal glands, which is termed the adrenal medulla.
Your adrenal medulla contains specialized cells called chromaffin cells, which release adrenaline (and noradrenaline) into the bloodstream in response to nerve stimulation.
- Adrenaline is produced by the innermost layer (medulla) of your adrenal glands.
What triggers adrenaline production?
As part of our fight or flight response, we activate a specialized network of nerves known as our sympathetic nervous system. This network runs up and down our spinal cord and branches out to several organs. Part of this network of sympathetic nerves feeds directly into the adrenal glands. We sometimes collate both the adrenal glands and sympathetic nervous system under the banner sympathoadrenal system.
When faced with a stressor, a part of your brain called the hypothalamus activates the sympathetic nervous system, including those nerves supplying the adrenal glands. These nerves then stimulate chromaffin cells in the adrenal medulla to release adrenaline into the bloodstream.
- Our sympathetic nervous system is a network of nerves that mediates our fight-or-flight response.
- Adrenaline is secreted by the adrenal glands in response to stimulation of the sympathetic nervous system.
How is adrenaline produced?
Adrenaline is derived from an amino acid called tyrosine.
Amino acids are the building blocks of protein and tyrosine is a non-essential amino acid (meaning it can be produced endogenously by the human body). We can make tyrosine by converting the amino acid phenylalanine, which in turn must be obtained from the diet as it an essential amino acid.
Within the adrenal glands, tyrosine is serially converted by various enzymes into different intermediary molecules, before ultimately being converted into adrenaline. Many of the enzymes responsible for producing adrenaline require another substance, called a cofactor, to function effectively.
Both the activity and availability of enzymes and cofactors can influence how well you synthesize adrenaline. As we’ll discover later, your genes can affect both these things.
- Adrenaline is derived from tyrosine.
- Tyrosine is converted into adrenaline in four stages.
- The activity of enzymes and cofactors during these stages influence your adrenaline levels.
Enzyme pathways involved in making adrenaline
Tyrosine --> L-DOPA
As the diagram shows, the first stage is the conversion of tyrosine into L-DOPA by the enzyme tyrosine hydroxylase (TH). This enzyme uses BH4 (tetrahydrobiopterin) as a cofactor. We’ve previously encountered BH4 in your BH4 Synthesis and Recycling Trait.
L-DOPA --> dopamine
The second stage of adrenaline synthesis sees L-DOPA converted into dopamine, which is a neurotransmitter in its own right. This reaction is catalysed by an enzyme called DOPA decarboxylase (also known as aromatic L-amino acid decarboxylase). It requires the active form of Vitamin B6, pyridoxal phosphate, as a cofactor.
Dopamine --> noradrenaline
Dopamine is next converted into another neurotransmitter, noradrenaline (norepinephrine), by the enzyme dopamine beta hydroxylase (DBH). DBH uses Vitamin C (ascorbate) as a cofactor. An adequate intake of Vitamin C in your diet is therefore important for producing adrenaline.
Noradrenaline --> adrenaline
In the final step, noradrenaline is turned into adrenaline by the enzyme phenylethanolamine N-methyltransferase (PNMT). This reaction requires a molecule called SAM (S-adenosyl methionine) as a cofactor.
Your PNMT enzyme is encoded by your PNMT gene. Interestingly, research shows that variations in the PNMT gene are associated with different levels of adrenaline in response to exercise.
How does adrenaline exert its effects in the body?
Adrenaline (and noradrenaline) work by binding to specialized receptors on the surfaces of cells known as adrenergic receptors.
There are two main classes of adrenergic receptor – alpha (α) and beta (β) receptors. Alpha (α) receptors can be further subdivided into α1 and α2 receptors, while beta (β) receptors can be further subdivided into β1, β2 and β3 receptors.
Adrenaline mainly binds to beta (β) receptors, but can also bind to and activate alpha (α) receptors.
When adrenaline binds to adrenergic receptors, it triggers a cascade of chemical reactions that go on to have various effects, depending on the type of receptor and the type of cell expressing that receptor.
For example, when adrenaline binds to β2 receptors on vascular smooth muscle in blood vessel walls, it causes the muscle to relax leading to vasodilatation and increased blood flow.
When adrenaline binds to β1 receptors on heart muscle, it speeds up our heart rate.
As we will explore in future traits, the effects of adrenaline in the body are also influenced by the quantity and activity of adrenergic receptors on cell surfaces.
- Adrenaline exerts its effects by binding to adrenergic receptors.
- Adrenaline mainly binds to and activates beta (β) adrenergic receptors.
How is adrenaline degraded?
Unlike other hormones (e.g. cortisol), adrenaline doesn’t inhibit its own production as part of a negative feedback cycle. Instead it is metabolized and broken down by enzymes in various tissues, including the liver and nerve tissue.
There are two key enzymes involved in the breakdown of adrenaline: COMT (catechol-O-methytransferase) and MAO (monoamine oxidase). Together these metabolize adrenaline into a molecule called vanillylmandelic acid (VMA).
The activity of your COMT and MAO enzymes partly determine the duration of adrenaline’s effects in the body. They also influence your baseline levels of adrenaline. In isolation, higher activity of your COMT and MAO enzymes may give rise to lower circulating levels of adrenaline.
As well as metabolizing adrenaline, these enzymes also degrade the other catecholamines (noradrenaline and dopamine).
- Adrenaline is broken down by two enzymes: COMT and MAO.
- The activity of COMT and MAO enzymes influences your baseline adrenaline levels.
Why are baseline adrenaline levels important?
Baseline adrenaline levels refer to the amount of adrenaline circulating in your bloodstream at rest (i.e. not during exercise, and not in response other stressors).
If levels of adrenaline rapidly rise as part of your fight-or-flight response to exercise, it’s understandable to ask why baseline adrenaline levels matter?
The simple answer is that your baseline adrenaline levels influence how quickly you can raise adrenaline levels to the amount required for beneficial effects during exercise.
Lower baseline circulating levels of adrenaline may therefore impair exercise performance.
Although higher baseline adrenaline levels may be linked to better exercise performance, long-term elevations of adrenaline may make you more susceptible to stress, anxiety and high blood pressure.
- Your baseline adrenaline levels affect your exercise response.
As described in the “How is adrenaline produced?” section, adrenaline is made from tyrosine in a series of chemical reactions. These chemical reactions are catalyzed (i.e. sped up) by various enzymes. It follows that the activity of these enzymes will affect how effectively we produce adrenaline. In this respect, variants of your PNMT gene influence your baseline levels of adrenaline.
Your PNMT gene encodes the PNMT enzyme responsible for converting noradrenaline into adrenaline. Variants of this gene may be linked to different activity of the PNMT enzyme, which in turn affects how effectively you convert noradrenaline into adrenaline.
Baseline levels of adrenaline are also affected by how effectively you clear and metabolize adrenaline. In this respect, variants of your COMT and MAO genes influence your baseline levels of adrenaline
Your COMT gene encodes the COMT enzyme that degrades adrenaline. Some variants of this gene are associated with reduced expression of the COMT enzyme. This may give rise to reduced breakdown of adrenaline and therefore higher baseline levels of adrenaline (as well as other catecholamines).
Similar to your COMT gene, variations in MAO genes (MAO-A and MAO-B) may affect the rate at which you degrade adrenaline and therefore influence baseline adrenaline levels.
- Variants of your PNMT genes affect how well you produce adrenaline.
- Variants of your COMT and MAO genes affect how well you clear adrenaline.
- Both the production and clearance of adrenaline affect your baseline adrenaline levels.