Trait overview: Nitric oxide and blood flow

Wednesday, April 01, 2020. Author Alex Auld

Trait overview: Nitric oxide and blood flow

As we exercise, or perform any strenuous task, our working muscles require more oxygen and glucose to continue contracting.

In other words, our muscles have greater energy demands and therefore must be supplied with more blood. In addition to providing additional oxygen and glucose, the increased blood flow also removes waste products such as carbon dioxide and lactic acid, which accumulate at a greater rate in working muscles.  

During exercise, studies suggest that blood flow to working muscles increases by as much as 50 to 100 times!


How do we increase blood flow to exercising muscles?

There are two main ways that we can increase blood flow to working muscles:

  1. Increased heart rate
  2. Vasodilation

While an increased heart rate certainly increases the amount of blood flowing through arteries at any given moment, it does not necessarily ensure that this blood is going to where it’s most needed – that’s where your blood vessels come in to play.

The walls of your arteries contain a special type of muscle called ‘vascular smooth muscle’.  When vascular smooth muscle contracts, the blood vessel narrows (vasoconstriction), allowing less blood to flow. By contrast, when it relaxes, the blood vessel widens (vasodilation), and more blood can flow through.

There are several different mechanisms by which vasodilation is triggered, some of which involve an important molecule called nitric oxide (NO)


What is nitric oxide (NO) and how is it produced?

Nitric oxide is a small signalling molecule produced by various cells in the body, including nerve cells in the brain (neurons), immune cells and vascular endothelial cells.

Vascular endothelial cells are found in the innermost lining of blood vessels, called the endothelium.

During exercise, nitric oxide produced by vascular endothelial cells diffuses outwards to the layer of vascular smooth muscle in blood vessel walls, causing the blood vessel to dilate and increase blood flow.


How is Nitric Oxide (NO) produced?

NO is made from the amino acid, L-arginine

As a non-essential amino acid, your body can produce L-arginine itself, but it is also found in various foods including turkey, spinach, soybeans and lentils.

To make NO, your vascular endothelial cells produce an enzyme called Nitric Oxide Synthase (NOS), which converts L-arginine into NO. For the NOS enzyme to produce NO effectively, it also requires other molecules (called cofactors), including BH4.

A by-product of NO formation is L-citrulline, another amino acid.

Interestingly, L-citrulline can be recycled back into L-arginine, which can then be used by NOS to produce more NO. This is why some athletes take L-citrulline supplements.


What causes nitric oxide (NO) production?

As we begin to exercise, our heart rate increases, causing blood to flow through blood vessels at a faster rate. In turn, this creates frictional force, known as shear stress, against the inner lining of the blood vessel wall. Shear stress stimulates vascular endothelial cells, activating the NOS enzyme, causing the rapid formation of NO.

Working muscles also produce a molecule called adenosine during exercise. When adenosine binds to specialised receptors on the surface of vascular endothelial cells, it further promotes NOS activity and consequently increases NO formation.

In addition to adenosine, your vascular endothelial cells also have receptors to other vasoactive molecules that all ultimately promote vasodilation, including acetylcholine, bradykinin and substance P.


Your Nitric Oxide and blood flow trait

At FitnessGenes, our team analyse and combine a number of genetic variants to determine whether you have good, average or reduced activity of NOS. These genetic variants include:


The NOS3 gene encodes the NOS enzyme. As NOS converts L-arginine into NO, your NOS activity directly influences your NO production and therefore how effectively your blood vessels dilate.


As explained earlier, the NOS enzyme requires cofactors to function efficiently, including BH4. The GCH1 gene is involved in the production and processing of BH4. Reduced BH4 production can therefore also limit NO production.

Other genes

The biological pathways associated with NO production are also intertwined with pathways regulating other processes, such as metabolism of folate, control of calcium levels and inflammation. As a result, genes involved in these processes will influence overall NO production.


Discover your personal trait

Discover your personal circulating NO levels, alongside other exercise-related traits including adrenaline level, mitochondrial biogenesis and cortisol sensitivity, by unlocking your unique genetic code with FitnessGenes. 

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