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. It affects nearly 1 in 2 Americans and remains as a contributing cause of death in the United States. There are many genetic and environmental factors involved with the development of hypertension including genetics, diet, and stress.
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. These hypertension-induced effects eventually lead to white matter lesions, which is the pathological basis for hypertension-induced cognitive impairment. 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. 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. 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. 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.
Salt-sensitive hypertension In terms of environmental factors, dietary salt intake is the leading risk factor in the development of hypertension. 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. In normal conditions, the body counteracts excessive salt intake by increasing cardiac output and expanding extracellular fluid volume. 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. Furthermore, it is estimated that 51% of people that are hypertensive are salt sensitive compared to 26% of people that are normotensive. Salt sensitivity is often associated with endothelial dysfunction due to reduced nitric oxide (NO) production and endothelial NO synthase activity, which impairs vasodilation. During sodium intake, an increased production of NO in the kidneys and peripheral vasculature is imperative for sodium balance and regulation of blood pressure.
Hypertension induced by angiotensin II
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. 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. 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. 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. 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. 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. Dysfunction of ion channels is also associated with impaired endothelial function.
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