Primary (Essential) Hypertension
There are two broad categories of hypertension - primary (or essential) and secondary hypertension. Approximately 90-95% of patients diagnosed with hypertension have primary hypertension. Unlike secondary hypertension, there is no known cause of primary hypertension. Therefore, the diagnosis of primary hypertension is made after excluding known causes that comprise what is called secondary hypertension.
Despite many years of active research, there is no unifying hypothesis to account for the pathogenesis of primary hypertension. There is a natural progression of this disease that suggests early elevations in blood volume and cardiac output might initiate subsequent changes in the systemic vasculature (increased resistance). This has suggested to some researchers that a basic underlying defect in many hypertensive patients is an inability of the kidneys to adequately handle sodium. Increased sodium retention could then account for the increase in blood volume. In chronic, long-standing hypertension, blood volume and cardiac output are often normal, therefore the hypertension is sustained by an elevation in systemic vascular resistance rather than by an increase in cardiac output. This increased resistance is caused by a thickening of the walls of resistance vessels and by a reduction in lumen diameters. There is also evidence for increased vascular tone. This could be mediated by enhanced sympathetic activity or by increased circulating levels of angiotensin II. In recent years, considerable evidence has suggested that changes in vascular endothelial function may cause the increase in vascular tone. For example, in hypertensive patients, the vascular endothelium produces less nitric oxide and the vascular smooth muscle is less sensitive to the actions of this powerful vasodilator. There may also be an increase in endothelin production, which can enhance vasoconstrictor tone. There is compelling evidence that hyperinsulinemia and hyperglycemia in type 2 diabetes (non-insulin dependent diabetes) causes endothelial dysfunction by enhanced oxygen free radical mediated damage and decreased nitric oxide bioavailability.
Many mechanisms may operate to initiate and sustain hypertension. Treatment of patients with primary hypertension is in reality a pharmacologic intervention to modify factors (e.g., angiotensin II, sympathetic activity, calcium entry into cells) in a way that leads to a reduction in arterial pressure. However, these treatments do not target the cause(s) of the underlying disease. Nevertheless, treatment of hypertension with antihypertensive drugs is vitally important because hypertension increases the risk for coronary artery disease, stroke, renal disease and other disorders. The three broad classes of drugs used to treat primary hypertension are diuretics (to reduce blood volume), vasodilators (to decrease systemic vascular resistance), and cardioinhibitory drugs (to decrease cardiac output).
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