Hypertension and the brain

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Hypertension graphic Hypertension-graphic-with-numbers.gif
Hypertension graphic

Hypertension is a condition characterized by an elevated blood pressure in which the long term consequences include cardiovascular disease, kidney disease, adrenal gland tumors, vision impairment, memory loss, metabolic syndrome, stroke and dementia. [1] It affects nearly 1 in 2 Americans and remains as a contributing cause of death in the United States. [2] There are many genetic and environmental factors involved with the development of hypertension including genetics, diet, and stress.

Contents

Complications of hypertension Complications of hypertension whitebackground.png
Complications of hypertension

The brain is one of the major organs affected by hypertension and recent findings have linked hypertension to various forms of cognitive decline. Not only does hypertension affect the cellular structure and molecular composition of blood vessels (arteries, veins, capillaries), it also affects their ability to regulate vital functions that are essential for healthy brain function such as oxygen and glucose delivery, cerebral environment control via the blood-brain barrier, and trafficking of immune cells and metabolic by-products. [3] These hypertension-induced effects eventually lead to white matter lesions, which is the pathological basis for hypertension-induced cognitive impairment. [4] A National Institute on Aging (NIA) study that measured cognition twenty years after measuring blood pressure showed that there was a 9% increase in risk for cognitive decline for every 10mmHg increase in systolic blood pressure. [5] Additionally, the Atherosclerosis Risk in Communities cognitive study shows that those with prehypertension or high blood pressure performed lower on processing speed, short-term memory, and executive function tests. [5] Hypertension is also a prominent risk factor for two major brain diseases: stroke and dementia, and accounts for approximately 50% of deaths caused by stroke or heart disease according to the World Health Organization (WHO).

Hypertension

Primary and secondary hypertension

Primary hypertension, also known as essential hypertension, is the result of a consistent elevation of the force of blood being pumped throughout the body, whereas secondary hypertension is the result of high blood pressure due to another medical condition.> Diseases that can cause secondary hypertension include diabetic nephropathy, glomerular disease, polycystic kidney disease, cushing syndrome, pheochromocytoma, aldosteronism, sleep apnea, obesity, and pregnancy. [6] Most often, there are no definite symptoms to this disease. There are some signs that one could look for to deduce it is secondary hypertension rather than primary such as sudden onset of hypertension before the age of 30 or after 55, no family history of hypertension, hypertension that does not respond to medication (resistant hypertension), and no signs of obesity. [6]

Salt-sensitive hypertension

In terms of environmental factors, dietary salt intake is the leading risk factor in the development of hypertension. [7] Salt sensitivity is characterized by an increase in blood pressure with an increase in dietary salt and is associated with various genetic, demographic, and physiological factors— African American populations, postmenopausal women, and older individuals carry a higher risk of developing salt sensitivity. [8] In normal conditions, the body counteracts excessive salt intake by increasing cardiac output and expanding extracellular fluid volume. [9] However, individuals who are salt-sensitive exhibit an over reactive sympathetic nervous system and are unable to suppress the renin-angiotensin axis as well as normotensive individuals, resulting in salt retention by the kidneys and increased vascular resistance and consequently, increased risk of developing hypertension. [9] Furthermore, it is estimated that 51% of people that are hypertensive are salt sensitive compared to 26% of people that are normotensive. [8]

Salt sensitivity is often associated with endothelial dysfunction due to reduced nitric oxide (NO) production and endothelial NO synthase activity, which impairs vasodilation. [8] During sodium intake, an increased production of NO in the kidneys and peripheral vasculature is imperative for sodium balance and regulation of blood pressure.[ citation needed ]

Hypertension induced by angiotensin II

Renin-angiotensin-aldosterone system (RAS) Renin-angiotensin-aldosterone system.svg
Renin-angiotensin-aldosterone system (RAS)

The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure, fluid and electrolyte homeostasis, and vascular resistance via release of hormones. The system is initiated by renin converting the precursor protein angiotensinogen into angiotensin I (Ang I). Ang I then gets converted to Ang II by the angiotensin-converting-enzyme (ACE) which then goes on to produce a number of different effects on the body. One such effect is inducing hypertension via Ang II and Ang metabolites produced by the degradation of Ang I and Ang II. [3] Ang II increases blood pressure by constricting blood vessels and it stimulates the production of aldosterone, which also increases blood pressure by increasing the volume of fluid in the body via increased sodium reabsorption by renal tubules in the kidney. Hypertension is associated with enhanced RAAS activity.[ citation needed ]

There are several Ang receptors in the body with the most common being AT1R, which is expressed in the heart, kidney, gut, blood vessels, and the brain. Ang II binds AT1R to produce vasoconstriction, inflammation, and endothelial dysfunction.[ citation needed ] Activation of AT2R has opposite effects of those to AT1R, exerting hypotensive effects.

Pathophysiology

Endothelial dysfunction

The endothelium plays a critical role in regulating blood vessels throughout the body, modulating the function of cells with the vessel walls and even non-vascular cells. For example, the endothelium releases cytokines and expresses adhesion molecules that recruit leukocytes, which is important in inflammation. [10] The endothelium influences vascular muscle by regulating vascular tone and it also determines vascular permeability into the tissues— tight junctions between endothelial cells are pertinent in the blood brain barrier. [11]

The endothelium secretes vasoconstrictive and vasodilative molecules that play a major role in controlling vascular tone and blood flow. Nitric oxide (NO) and prastacyclin are the main vasodilatory molecules and an impairment or reduction of the molecules activity and/or production is the main cause of endothelial dysfunction. In models of Ang II-dependent hypertension, endothelium-dependent vasodilation is reduced. [3] Dysfunction of ion channels is also associated with impaired endothelial function.[ citation needed ]

Arterial stiffness

Arteries are blood vessels that carry blood away from the heart to other areas of the body. They are mainly responsible for transporting oxygen and nutrients to various parts of the body and removing carbon dioxide and wastes. Arteries are generally elastic, which allows them to bend and fit throughout the body and maintain a stable blood pressure. [12] Arterial stiffness occurs as people age and increases the risk of stroke and cardiovascular diseases. Elastin and collagen are of the major determinants of arterial stiffness as well as matrix metalloproteases, advanced glycation endproducts (AGE), inflammation, neuroendocrine signaling, and genetics. [12] [13] The more stiff arteries are, the more pressure the heart needs to exert to pump blood throughout the body and therefore, the higher blood pressure a person has. [14]

Blood brain barrier Blood vessels brain english.jpg
Blood brain barrier

Blood–brain barrier dysfunction

The blood–brain barrier (BBB) is essential in maintaining a homeostatic environment for neurons and glial cells by preventing solutes from diffusing into the brain interstitial space. The endothelial cells that makeup the BBB are different from those that make up the vasculature structurally, molecularly, and metabolically. They are connected by tight junctions, which further ensure that molecules do not freely pass through.[ citation needed ]

BBB disruption is associated with hypertension, cerebrovascular diseases, neurodegenerative diseases, and aging.[ citation needed ]

Inflammation

Inflammation can impair vascular function and therefore cause many of the pathophysiologies mentioned above. Hypertension is accompanied by peripheral inflammation, which can affect CNS function through activation of circumventricular organs (CVOs). Furthermore, Ang II also plays a role in the neural control of blood pressure through the activation of these CVOs. [3] More recently, hypertension is recognized as an immune condition. [15] Chronic inflammation, compromises the BBB, which in turn allows for molecules to leak into the CNS. This then activates astrocytes and microglia, causing an immune response within the brain. Neuroinflammation can reach regulatory centers of blood pressure such as the paraventricular nucleus (PVN), leading to enhanced sympathoexcitation, and ultimately to a sustained elevation of blood pressure. [15] The most common neuroinflammatory markers are interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). [15]

Cerebral artery structure and function

Hypertension, mainly through Ang II, remodels vessel structure and function by increasing oxidative stress, vascular inflammation, and altering cerebral blood flow. [3] Hypertension causes a reduction in the lumen diameter of cerebral arteries, which increases its vascular resistance. The brain receives around 15–20% of the total cardiac output and therefore, disruptions in this cerebral perfusion have damaging effects to proper neuronal function. [16]

Encephalopathies

Hypertension and stroke

CT scan of two lacunar infarctions. Moments after an ischemic stroke, lesions are established that can be detected. CT of lacunar strokes.jpg
CT scan of two lacunar infarctions. Moments after an ischemic stroke, lesions are established that can be detected.

Hypertension is the leading cause of strokes and studies show that it increases the risk of a stroke by 220% [17] [18] and stroke is the leading cause of long-term disability. [19] High blood pressure weakens arteries (small vessel disease) and causes blood vessels to be more likely to clog and/or burst. A lacunar infarction occurs when an artery is blocked and an intracerebral hemorrhage occurs when the blood vessels burst. In turn, the brain is more vulnerable to ischemic insults as there is a dysregulation in the supply of blood and oxygen. [19] More specifically, hypertension inflicts damage to small resistance arteries, which supply nutrients to the internal capsule, brainstem, thalamus, cerebellum, and basal ganglia, and cause cell death and tissue degeneration. [3] Blood clots also accelerate arterioscelerosis, which causes arteries to thicken and harden. [20] Essentially, hypertension is the biggest risk factor for stroke and tissue damage caused by a stroke is a major risk factor for cognitive decline, therefore the risk of stroke may act as a mediator in the relationship between blood pressure and cognition. [21] Besides lifestyle modifications, blood pressure control is the #1 treatment for stroke prevention. Antihypertensive medication show a protective effect against stroke-related cognitive impairments. [3]

CT scan of intracerebral hemorrhage Intracerebral hemorrage (CT scan).jpg
CT scan of intracerebral hemorrhage

Hypertension→ Small vessel disease → Lacunar infarction & Intracerebral hemorrhage → Tissue damage[ citation needed ]

Hypertension and vascular dementia

Vascular dementia develops as blood vessels in the brain become damaged, preventing brain cells from receiving the nutrients it needs to function. [18] Hypertension alters the brain's vasculature via inadequate blood flow, leading to changes in the blood-brain barrier (BBB) and cerebral blood flow and ultimately, weakening brain structures and functions. [3] Vascular dementia is characterized by ischemic infarcts, cerebral hemorrhages, white matter lesions, BBB dysfunction, and/or microvascular degeneration. [22]

Multiple longitudinal and cross-sectional studies showed that hypertension is a prevalent risk factor of vascular dementia in participants ranging from 58~90 years old. [23] Moreover, a meta-analysis on the longitudinal and cross-sectional studies showed that hypertensives are 59% more likely to develop vascular dementia compared to those that are normotensive. [23]

Hypertension and Alzheimer's disease

Although there are no direct correlations with hypertension and its association with Alzheimer's disease, chronic hypertension is associated with white matter lesions, lacunar infarcts, neurotic plaques and neurofibrillary tangles, all pathological features of AD. [3]

A 1993 Framingham study showed that untreated blood pressure is inversely related to cognitive function in stroke-free adults aged 55–88. [24] Furthermore, a longitudinal clinical trial study paired with secondary data analysis from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) interventional trial revealed that hypertensives had a faster decrease in frontally-mediated cognitive functions such as reasoning abilities. [25] Many studies show correlations with hypertension and cognitive decline however, some studies do not such as the Chicago Health and Aging Project, which states that blood pressure is not associated with cognitive function. [26]

Current treatments

Lifestyle modifications

Antihypertensive agents Antihypertensive agents1.pdf
Antihypertensive agents

Pharmacological intervention

Multiple studies suggest that hypertension is a prevailing factor in the development and progression of age-related cognitive decline and that antihypertensive approaches could help control or relieve the impact of hypertension on cognition.[ citation needed ]

A meta-analysis of randomized controlled studies from 1970 to 2012 showed that lowering blood pressure via antihypertensive medications is associated with a reduction in heart failure and stroke risk. [27] Additionally, an Epidemiology of Vascular Aging (EVA) study showed that participants with high blood pressure exhibited 4 points lower on the Mini-Mental State Evaluation (MMSE) which correlates to these participants being 4.3 times more likely to exhibit cognitive decline and that the risk decreased to 1.9 times in those taking antihypertensive medication. [28] However, it is still up to debate on whether antihypertensive medications have an impact on cognitive decline. A randomized double blind study by the Systolic Hypertension Study in Europe revealed that the incidence of dementia was lowered by 50% in participants that were given pharmacological intervention for hypertension after 2 years and that there was a 55% decrease in the individuals developing Alzheimer's disease and vascular dementia. [29] The pharmacological drugs included nitrendipine (calcium-channel blocker), enalapril (ACE inhibitor), and hydrochlorothiazide (diuretic). Various studies looking at different classes of antihypertensive medication including ARBs, beta-blockers, diuretics, and ACE inhibitors, reveal that pharmacological treatments have overall cerebroprotective effects however, the effects vary depending on drug class and its mechanisms. [30] [31] [32]

Angiotensin-converting enzyme inhibitors

Angiotensin-converting enzyme (ACE) inhibitors essentially block the conversion of Ang I to Ang II. They cause relaxation of the blood vessels as there are less Ang II molecules (vasoconstrictor) circulating, increase natriuresis, decrease blood volume, all of which culminate in lowering blood pressure. Enalapril, Benazepril, Perindopril, and Ramipril are among commonly prescribed ACE inhibitors clinically.[ citation needed ]

Angiotensin receptor blockers

Angiotensin receptor blockers (ARBs) antagonize the action of Ang II by binding and inhibiting angiotensin II type 1 receptor. In doing so, ARBs block vasoconstriction, promote natriuresis, and reduce oxidative stress. Studies show that the vasodilator ability of vessels are impaired in hypertensives which causes brain perfusion to decrease significantly, influencing cognitive function. ACEs and ARBs improve cerebral perfusion in hypertensive patients. [31] Losartan, Irbesartan, Valsartan, Olmesartan, and Azilsartan, are common ARBs that are clinically available.[ citation needed ]

Angiotensin type 2 receptor agonists

AT2R agonists cause vasodilation, exerting hypotensive effects. In animal models of ischemia, activation of AT2R is protective as it reduces the infarct area by increasing cerebral perfusion, decreases superoxide production, and promotes neuronal cell differentiation and neuritis growth, which all come together to reduce axonal degeneration and inflammation.[ citation needed ]

Beta-blockers Non-selective beta blocker.svg
Beta-blockers

Beta-blockers

Beta-blockers are competitive antagonists of the adrenergic beta receptor, blocking the binding sites of epinephrine and norepinephrine. They lower blood pressure by a RAAS independent mechanism, reducing plasma renin activity and Ang II levels. Propranolol, Atenolol, Bupranolol, Timolol, are some examples of clinically available beta-blockers[ citation needed ].

Related Research Articles

<span class="mw-page-title-main">Blood pressure</span> Pressure exerted by circulating blood upon the walls of arteries

Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" refers to the pressure in a brachial artery, where it is most commonly measured. Blood pressure is usually expressed in terms of the systolic pressure over diastolic pressure in the cardiac cycle. It is measured in millimeters of mercury (mmHg) above the surrounding atmospheric pressure, or in kilopascals (kPa). The difference between the systolic and diastolic pressures is known as pulse pressure, while the average pressure during a cardiac cycle is known as mean arterial pressure.

<span class="mw-page-title-main">Hypertension</span> Long-term high blood pressure in the arteries

Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide.

<span class="mw-page-title-main">Vascular dementia</span> Dementia resulting from stroke

Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dementia include subcortical vascular dementia, multi-infarct dementia, stroke-related dementia, and mixed dementia.

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

<span class="mw-page-title-main">Microangiopathy</span> Medical condition

Microangiopathy is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to macroangiopathies such as atherosclerosis, where large and medium-sized arteries are primarily affected.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Cerebral edema</span> Excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain

Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

Essential hypertension is a form of hypertension without an identifiable physiologic cause. It is the most common type affecting 85% of those with high blood pressure. The remaining 15% is accounted for by various causes of secondary hypertension. Essential hypertension tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors. Hypertension can increase the risk of cerebral, cardiac, and renal events.

<span class="mw-page-title-main">Perivascular space</span>

A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role for neural and blood-derived messengers. The brain pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. In the brain, perivascular cuffs are regions of leukocyte aggregation in the perivascular spaces, usually found in patients with viral encephalitis.

<span class="mw-page-title-main">Hypertensive emergency</span> Very high blood pressure and signs of organ damage

A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems. It is different from a hypertensive urgency by this additional evidence for impending irreversible hypertension-mediated organ damage (HMOD). Blood pressure is often above 200/120 mmHg, however there are no universally accepted cutoff values.

<span class="mw-page-title-main">Arteriolosclerosis</span> Medical condition

Arteriolosclerosis is a form of cardiovascular disease involving hardening and loss of elasticity of arterioles or small arteries and is most often associated with hypertension and diabetes mellitus. Types include hyaline arteriolosclerosis and hyperplastic arteriolosclerosis, both involved with vessel wall thickening and luminal narrowing that may cause downstream ischemic injury. The following two terms whilst similar, are distinct in both spelling and meaning and may easily be confused with arteriolosclerosis.

Hypertensive encephalopathy (HE) is general brain dysfunction due to significantly high blood pressure. Symptoms may include headache, vomiting, trouble with balance, and confusion. Onset is generally sudden. Complications can include seizures, posterior reversible encephalopathy syndrome, and bleeding in the back of the eye.

Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke patients. It has been found to be effective for the treatment of pulmonary hypertension. It has been demonstrated that fasudil could improve memory in normal mice, identifying the drug as a possible treatment for age-related or neurodegenerative memory loss.

Lipohyalinosis is a cerebral small vessel disease affecting the small arteries, arterioles or capillaries in the brain. Originally defined by C. Miller Fisher as 'segmental arteriolar wall disorganisation', it is characterized by vessel wall thickening and a resultant reduction in luminal diameter. Fisher considered this small vessel disease to be the result of hypertension, induced in the acute stage by fibrinoid necrosis that would lead to occlusion and hence lacunar stroke. However, recent evidence suggests that endothelial dysfunction as a result of inflammation is a more likely cause for it. This may occur subsequent to blood–brain barrier failure, and lead to extravasation of serum components into the brain that are potentially toxic. Lacunar infarction could thus occur in this way, and the narrowing – the hallmark feature of lipohyalinosis – may merely be a feature of the swelling occurring around it that squeezes on the structure.

<span class="mw-page-title-main">Pathophysiology of hypertension</span>

Pathophysiology is a study which explains the function of the body as it relates to diseases and conditions. The pathophysiology of hypertension is an area which attempts to explain mechanistically the causes of hypertension, which is a chronic disease characterized by elevation of blood pressure. Hypertension can be classified by cause as either essential or secondary. About 90–95% of hypertension is essential hypertension. Some authorities define essential hypertension as that which has no known explanation, while others define its cause as being due to overconsumption of sodium and underconsumption of potassium. Secondary hypertension indicates that the hypertension is a result of a specific underlying condition with a well-known mechanism, such as chronic kidney disease, narrowing of the aorta or kidney arteries, or endocrine disorders such as excess aldosterone, cortisol, or catecholamines. Persistent hypertension is a major risk factor for hypertensive heart disease, coronary artery disease, stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease.

<span class="mw-page-title-main">Complications of hypertension</span>

Complications of hypertension are clinical outcomes that result from persistent elevation of blood pressure. Hypertension is a risk factor for all clinical manifestations of atherosclerosis since it is a risk factor for atherosclerosis itself. It is an independent predisposing factor for heart failure, coronary artery disease, stroke, kidney disease, and peripheral arterial disease. It is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries.

A silent stroke is a stroke that does not have any outward symptoms associated with stroke, and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain and places the patient at increased risk for both transient ischemic attack and major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being amongst the predisposing factors.

<span class="mw-page-title-main">20-Hydroxyeicosatetraenoic acid</span> Chemical compound

20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.

<span class="mw-page-title-main">Neurovascular unit</span>

The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons. The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times. Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly.

References

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  2. ↑ CDC (2020-09-08). "Facts About Hypertension | cdc.gov". Centers for Disease Control and Prevention. Retrieved 2020-10-19.
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  4. ↑ Sierra, Cristina; Coca, Antonio (2006-04-21). "White Matter Lesions and Cognitive Impairment as Silent Cerebral Disease in Hypertension". The Scientific World Journal. 6: 494–501. doi: 10.1100/tsw.2006.99 . ISSN   2356-6140. PMC   5917262 . PMID   16633699.
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  29. ↑ Forette, F.; Seux, M. L.; Staessen, J. A.; Thijs, L.; Birkenhäger, W. H.; Babarskiene, M. R.; Babeanu, S.; Bossini, A.; Gil-Extremera, B.; Girerd, X.; Laks, T. (1998-10-24). "Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial". Lancet. 352 (9137): 1347–1351. doi:10.1016/s0140-6736(98)03086-4. ISSN   0140-6736. PMID   9802273. S2CID   20693800.
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