This chapter discusses mechanisms of physiological regulation of blood pressure (BP) and pathophysiological changes that lead to hypertension. Long-term control of BP occurs via the renal-body fluid feedback system, which involves pressure natriuresis—the high-BP-induced increase in sodium and water excretion by the kidney that leads to a reduction of the BP. Impaired pressure natriuresis can result from impaired renal function, altered activation of hormones that regulate salt and water excretion by the kidney (such as those in the renin-angiotensin-aldosterone system), or excessive activation of the sympathetic nervous system (see accompanying Hurst's Central Illustration). In hypertensive individuals, increased BP is sustained by a shift of pressure natriuresis such that a sodium balance is maintained at higher BP; therefore, effective treatment requires the resetting of pressure natriuresis toward normal BP. This resetting can be achieved by increasing renal excretory capability (for example, by using diuretics) or by reducing antinatriuretic influences on the kidney (for example, using inhibitors of the renin-angiotensin-aldosterone system).
Hurst's Central Illustration: Pathophysiology of Hypertension
The pathophysiology of hypertension involves the impairment of renal pressure natriuresis, the feedback system in which high blood pressure induces an increase in sodium and water excretion by the kidney that leads to a reduction of the blood pressure. Pressure natriuresis can result from impaired renal function, inappropriate activation of hormones that regulate salt and water excretion by the kidney (such as those in the renin-angiotensin-aldosterone system), or excessive activation of the sympathetic nervous system.
More than 1 billion individuals worldwide, including at least 70 million Americans, have high blood pressure (BP) warranting some form of treatment.1,2,3,4 Higher-than-optimal BP is the largest contributor to global mortality, and approximately 9.4 million deaths per year are attributed to uncontrolled hypertension.2,3,4 As life expectancy continues to increase, hypertension will become an even more important medical and public health issue because BP typically increases with aging in most industrialized countries. In the United States, 50% of people 60 to 69 years of age and approximately 75% of people 70 years or older have hypertension.3 In some nonindustrialized populations, however, BP does not rise with increasing age, and only a small fraction of the population develops hypertension. This suggests that predisposing environmental factors play a major role in causing hypertension and that an increase in BP with aging is not inevitable when these factors are absent.
A direct positive relationship between BP and cardiovascular disease (CVD) risk has been observed in men and women of all ages, races, ethnic groups, and countries, regardless of other risk factors for CVD.1 Observational studies indicate that death from CVD increases progressively and linearly as BP increases above 115 mm Hg systolic and 75 mm Hg diastolic.1 For every 20 mm Hg increase in systolic BP ...