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Arterial Hypertension Health Article

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Mechanisms Of Hypertension

In 95% of hypertensive patients in general practice, a single reversible cause of the elevated blood pressure cannot be identified, hence the term primary hypertension . However, in most patients with primary hypertension, readily identifiable behaviors—habitually excessive consumption of calories, salt, or alcohol—contribute importantly to the elevated blood pressure. In the remaining 5%, a more discrete mechanism can be identified, and the condition is termed secondary hypertension . At the organ-system level, hypertension can result from a gain in function of pathways that promote vasoconstriction and renal retention of salt and water and/or a loss in function of pathways that promote vasodilatation and renal excretion of salt and water.

BEHAVIORAL DETERMINANTS OF HUMAN BLOOD PRESSURE VARIATION.

The most important behavioral determinants of blood pressure are related to dietary consumption of calories and salt. In all populations studied, the prevalence of hypertension increases linearly with body mass index. With the rapidly growing incidence of obesity in industrialized societies, reaching epidemic proportions in the United States, increasing attention is being paid to the metabolic syndrome that often accompanies hypertension. The metabolic syndrome refers to the frequent clustering of hypertension with abdominal ("male-pattern") adiposity, insulin resistance, and a dyslipidemic pattern consisting typically of elevated plasma triglyceride and low high-density lipoprotein (HDL) cholesterol levels. Although the causal links remain to be elucidated, this constellation of metabolic abnormalities dramatically increases cardiovascular risk. In the Framingham Heart Study, obesity has been estimated to account for 50 to 60% of the new cases of hypertension. The underlying mechanisms by which weight gain leads to hypertension are incompletely understood, but there is mounting evidence for an expanded plasma volume plus sympathetic overactivity. The latter is thought to be a compensatory attempt to burn fat but at the expense of peripheral vasoconstriction, renal salt and water retention, and hypertension. In some obese individuals, sleep apnea is an important cause of hypertension. Repeated arterial desaturation sensitizes the carotid body chemoreceptors, causing sustained sympathetic overactivity.

Dietary sodium intake is another key behavioral determinant of human hypertension. The epidemiologic, clinical, and experimental support for this association is strong. In the Intersalt Study of 52 locations around the world, the risk of developing hypertension over three decades of adult life was linearly and very tightly related to dietary sodium intake. Dietary sodium reduction and diuretics have proved to be effective treatments for primary hypertension. However, both normotensive and hypertensive persons show tremendous interindividual variability in their blood pressure responses to dietary sodium loading and sodium restriction. This variability, which has led to some questioning about the "salt hypothesis," indicates a strong genetic underpinning.

GENETIC DETERMINANTS OF HUMAN BLOOD PRESSURE VARIATION.

The familial aggregation of hypertension documents an important genetic component. Concordance of blood pressures is greater within families than in unrelated individuals, greater between monozygotic than between dizygotic twins, and greater between biological than between adoptive siblings living in the same household. About 70% of the familial aggregation of blood pressure is attributed to shared genes rather than shared environment. Thus, hypertension can be viewed as a maladaptative interplay between the human genome and modern society. However, very little is known about the genetic determinants of blood pressure variation in the general population. The number of sequence variations, the specific loci, and their individual and combined effects remain conjectural.

In contrast, dazzling genetic research has elucidated the molecular mechanisms by which rare forms of human hypertension and hypotension are inherited as Mendelian traits. Mutations have been identified in eight genes that cause Mendelian forms of hypertension and in nine genes that cause Mendelian forms of hypotension. In every case, the mechanism involves the renal handling of salt and water and emphasizes the pivotal importance of the renin-angiotensin-aldosterone system in human blood pressure regulation. The Mendelian forms of hypertension altogether are responsible for a very small portion of the 50 million cases of hypertension in the United States. The Mendelian hypotensive and hypertensive traits represent the extremes of human blood pressure variation, and the key question is whether milder mutations in any of these 17 genes, alone or in combination, confer resistance against or sensitivity to the hypertensive effects of the common environmental exposures in the general population.

Clinical Manifestations

Hypertension has been termed the "silent killer," a chronic illness with a long asymptomatic phase that, if undetected and untreated, silently damages the heart, brain, and kidneys. Although headaches are common in patients with mild-to-moderate hypertension, episodes of headaches do not correlate with fluctuations in ambulatory blood pressure but rather with a person's awareness of his or her diagnosis.