Despite major advances in understanding the pathophysiology of
hypertension and availability of effective and safe
antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic
hypertension. Impaired renal-pressure natriuresis and chronic
hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of
salt and water; these factors include excessive activation of the
renin-
angiotensin-
aldosterone and sympathetic nervous systems, increased formation of
reactive oxygen species,
endothelin, and inflammatory
cytokines, or decreased synthesis of
nitric oxide and various
natriuretic factors. In human primary (
essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive
weight gain and dietary factors appear to play a major role since
hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to
hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of
hypertension.