ADRA1A Receptors: Blood vessel reactions under stress

Blood pressure and heart rate regulation are complex and fascinating. Our bodies have multiple ways of increasing or decreasing blood flow, depending on whether we are relaxed, exercising, stressed — or diving into the water.

We need oxygen and blood flow to the brain, heart, and lungs at all times, and when we are under stress, blood flow is prioritized for these crucial organs.

This article digs into one aspect of regulating blood flow via adrenergic receptors when under stress. I’ll touch on what happens when you dunk your face in water (diving reflex), the causes of fainting, blood pressure under stress, and how genetic variants influence your responses. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.

Alpha-1 Adrenergic receptor: heart rate and vascular constriction

Adrenergic receptors are a class of receptors that bind with catecholamines, such as epinephrine (adrenaline) and norepinephrine (noradrenaline). When a catecholamine binds to these receptors, it generally stimulates the sympathetic nervous system (fight-or-flight).[ref]

There are several types of adrenergic receptors, most of which act to either activate or relax muscles.

The α₁-adrenergic receptors (ADRA1A) are essential in how the muscles surrounding your blood vessels contract to change blood pressure and flow. These muscles are called the vascular smooth muscles.

ADRA1A receptors are also important in the control of heart rate, as well as the gastrointestinal and urinary system sphincters.[ref]

We have many systems in place to control blood pressure and heart rate. The α₁-adrenergic receptors react to epinephrine (adrenaline) and norepinephrine (noradrenaline) to control blood vessel reactivity when stressed.

But that is only part of the story with α₁-adrenergic receptors. Researchers recently discovered they are also important in cognitive function and neurotransmission.[ref]

Blood pressure:

Alpha-1 adrenergic receptor activation causes blood vessels to constrict. For example, if you are stressed out and produce a bunch of adrenaline (epinephrine), your blood vessels in your extremities will constrict, and your blood pressure will rise. The vasoconstriction in your extremities is why your hands and even your face may look pale when you have had a shock or stress. All the blood is being prioritized to go to the heart, brain, and lungs.

You may be somewhat familiar with the alpha-1 adrenergic receptor when it comes to blood pressure medications. Commonly called alpha blockers, blood pressure medications, such as doxazosin, that target the alpha-1 adrenergic receptors have been available for decades. Just like the name implies, alpha blocker are going to block the alpha-1 adrenergic receptor, preventing blood pressure from rising due to catecholamine release.

There is more to this adrenergic receptor story, though, than just blood pressure medicine.

Diving Reflex and Oxygen:

We have an innate reflex that kicks in when going underwater. Called the ‘diving reflex’, this automatic reflex causes babies to hold their breath underwater — and to a lesser extent, applies to the changes in adults as well.

Essentially, the diving reflex is a way mammals save oxygen when underwater through constriction of peripheral blood vessels, redistribution of blood flow to vulnerable organisms, a decrease in heart rate (bradycardia), release of red blood cells from the spleen, and usually an increase in blood pressure. This same reflex happens whether completely submerged in water or just dunking your face into a bowl of cold water. Water going up the nose triggers the trigeminal nerve and the diving reflex.

The constriction of blood vessels in the diving reflex is due to catecholamines binding to the ADRA1A receptor.

A recent study in adults who were not trained in diving looked at how ADRA1A genetic variants affect the diving reflex. The study found that participants with the variant had less vasodilation and, therefore, less blood flow to the lungs when diving.[ref]

Syncope (Fainting)

Fainting (also called syncope) can be caused by a lack of blood flow to the brain.

Vasovagal syncope is fainting caused by abnormal autonomic control of blood circulation. Essentially, the normal regulation of blood circulation is out of wack. The parasympathetic nervous system is overactivated and causes low arterial blood pressure and low blood flow to the brain.[ref]

What triggers vasovagal syncope (fainting)?

Orthostatic stress (standing up), emotional stress, medical manipulations — all can cause autonomic reactions such as flushing and nausea, followed by passing out.[ref]

Genetic variants in the ADRA1A gene (listed below) are linked to an increased risk of vasovagal syncope. Fainting was also a side effect of the initial alpha-blocker medications that became available in the 1970s.[ref]

Long Covid, Spike Protein, and Adrenergic Receptors:

Recently, researchers found that patients with long Covid are more likely to have autoantibodies targeting adrenoceptors – specifically β2- and α1-adrenoceptors.[ref]

Antibodies targeting the α1-adrenoceptors could explain some of the issues with heart rate, POTS, and cognition in people with long Covid or post vaccination.

POTS (postural orthostatic tachycardia syndrome) is also linked in studies to autoantibodies targeting the alpha-1 adrenergic receptor. A 2019 study found that 89% of the POTS patients had autoantibodies to the alpha-1 adrenergic receptors and that most of the patients had developed POTS following a viral infection.[ref]

Pain syndromes and peripheral nerve injury:

In some patients with complex regional pain syndrome, alpha-1 adrenergic receptors are overexpressed, compared to a normal control group. The activation of the alpha-1 adrenergic receptors in the epidermal (skin) cells causes an increase in IL-6, an inflammatory mediator. [ref]

When a nerve is injured, mast cells, white blood cells, and fibroblasts move to the site of injury to start the repair process. Research also shows that alpha-1 adrenoceptors are increased in areas of peripheral nerve injuries.[ref]

Neurological Conditions

Alpha-1 adrenergic antibodies are found at higher levels in people with Alzheimer’s than in people without Alzheimer’s. One study found that 59% of Alzheimer’s dementia patients had alpha-1 and beta-2 adrenergic receptor antibodies, compared to only 17% in an age-matched control group with neurological impairments other than Alzheimer’s or vascular dementia. The study’s authors link the adrenergic receptor antibodies to changes in blood flow to the brain.[ref]

Another study explains why autoantibodies to alpha-1 adrenergic receptors could cause dementia. The researchers explain that the autoantibodies bind to the receptor and cause a chronic activation that raises intracellular calcium levels. “An animal model has shown that agAAB [alpha-1 adrenoceptor agonistic antibodies] causes macrovascular and microvascular impairment in the vessels of the brain. Reduction in blood flow and the density of intact vessels was significantly demonstrated.”[ref]

Colon contractions

The ADRA1A receptors are also found in the muscles surrounding the colon. Norepinephrine release inhibits colonic contractions when binding to ADRA1A.[ref] This is one way that stress affects your gastrointestinal health on an acute basis.

ADRA1A Genotype Report

The following genetic variants have been associated with outcomes that illustrate the various functions of ADRA1A. For example, some variants are linked to blood vessel response to stress, and others are connected to cognitive changes.

Check your genetic data for rs1048101 (23andMe v4, v5; AncestryDNA):

G/G: arg/arg (most common genotype in all population groups – except Caucasians) more likely to faint with vagal syncope[ref], lower peripheral vascular response to cold in men, higher increase in heart rate with stress in women[ref], greater desire and response to cocaine[ref]
A/G: typical heart rate variability, typical risk of fainting; less vasodilation in lungs with diving reflex
A/A: cys/cys lower heart rate variability while lying down[ref], less vasodilation in lungs with diving reflex[ref], higher systolic blood pressure[ref]

Members: Your genotype for rs1048101 is —.

Check your genetic data for rs486179 (23andMe v4):

C/C typical
C/T: associated with increased risk of heroin addiction
T/T: associated with increased risk of heroin addiction[ref]

Members: Your genotype for rs486179 is —.

Check your genetic data for rs3730287 (23andMe v4; AncestryDNA):

C/C: increased risk of memory impairment after heroin use disorder[ref]
C/G: increased risk of memory impairment after heroin use disorder
G/G: typical

Members: Your genotype for rs3730287 is —.

Check your genetic data for rs17426222 (23andMe v4; AncestryDNA):

C/C: typical
C/T: typical risk
T/T: increased risk of generalized anxiety disorder[ref]

Members: Your genotype for rs17426222 is —.

Lifehacks:

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