Arterial hypertension occurs when changes develop that alter the relationship between blood volume and total peripheral resistance. For many of the secondary forms of hypertension, these factors are resonably well understood as, for example in so called renovascular hypertension. In this condition renal artery stenosis causes decreased glomerular flow and pressure in the afferent arteriole of the glomerulus and induces renin secretion by the juxtaglomerular cells. This initiates angiotension II-induced vasoconstriction; increased peripheral resistance; and through the aldosterone mechanism, increased sodium reabsorption and increased blood volume. Similarly in pheochromocytoma and tumor of the adrenal medula, catecholamines produced by tumor cells cause episodic vasoconstriction and thus induce hypertension.

Genetic factor

It is now thought that essential hypertension results from an interaction of genetic and environmental factors that affect cardiac output peripheral resistance or both. A generally accepted concept is that blood pressure (similar to height and weight) is a continiously distributed variable and that essential hypertension is one extreme of this distribution rather than a distinct disease. Gnetic factors clearly play a role in determining blood pressure levels, as evidenced by studies comparing blood pressure in monozygotic and dizygotic twins, studies of familial aggregation of hypertension compairing the blood pressure of biologic and adoptive siblings, and adoption studies. Although single-gene disorders can be responsible for hypertension in unusual cases, it is unlikely essential hypertension. It is more likely that essential hypertension is a polygenic and heterogeneous disorder in which the combined effect of mutations or polymorphisms at several gene loci influence blood pressure

Single gene disorders are known to cause relatively rare forms of hypertension through several mechanisms These include:

Gene defects in enzymes involved in aldosterone metabolism. These lead to an adaptive increase in secreation of aldosterone, increased salt ad ultimately hypertension. Mutations in proteins that affect sodium reabsorption. For example, mutations in an epithelial sodium channel protein lead to increased distal tubular reabsorption of sodium induced by aldosterone, resulting in a moderately severe form of salt-sensitive hypertension called Liddle syndrome.

Inherited variations in blood pressure may also depend on the cumulative effects of allelic forms of several genes that affect blood pressure. For example predisposition to essential hypertension has been associated with heterogeneity of the genes encoding components of the renin angiotension system: there is an association of hypertension with polymorphism in both the angiotensinogen locus and the angiotensin II type I receptor locus. Genetic variants in the renin angiotension system may contribute to the known racial differences in blood pressure regulation.

Environmental Factors

Environmental factors are thought to contribute to expression of the genetic determinants of increased pressure. The role of environment is illustrated by the lower incidence of hypertension chinese people living in china as compared with persons chinese descent living in the United States, Stress, obesity, smoking, physical inactivity and heavy consumption of salt have all been implicated as exogenous factors in hypertension.

Mechanisms

Renal Retension of Excess Sodium

The studies on the single gene disorder and renin angiotension system genes discussed previously have been imterpreted to favor the hypothesis that defects in renal sodium homeostasis are the primary cause of hypertension. Such scenarios suggest the existence genetic factors that result in reduced renal sodium excretion in the presence of normal arterial pressure as the initiating event. Decreased sodium excretion leads to an increase in fluid volume and a high cardiac output. In the fact of increasing cardiac output peripheral vasoconstriction occurs (as a result of autoregulation) to prevent the overperfusion of tissues that would ensue from an unchecked increase in cardiac output.

Autoregulation leads to increased peripheral resistance, however, and along with it an elevation of blood pressure. At the higher setting of blood pressure enough additional sodium can be excreted by the kidneys to equal intake and prevent fluid retension.

The evidence supporting the imprtance of sodium homeostasis in hypertension is as follows:

Rise in blood pressure with age is directly correlated with increasing levels of sodium intake.

People who consume little sodium have little or no hypertension, but when they consume more sodium hypertension appears.

Generally predisposed animals given sodium loads develop hypertension

Some individuals given large sodium loads over short periods develop an increase in vascular resistance and blood pressure.

Increased sodium is present in the vascular tissue and blood cells of most hypertensives.