Emerging concepts in the pathophysiology and treatment of obesity-associated hypertension.

The dramatic increase in the prevalence of obesity is a global phenomenon associated with increased risk of the development of cardiovascular and renal disease. Changes in renal structure and function that occur early in the development of obesity may lead to urine outflow obstruction and increased intrarenal pressure, mechanisms sufficient to shift the pressure-natriuresis relation to higher blood pressure levels. Another important alteration that may lead to hypertension with obesity is the increase in sympathetic nervous system activity. Several studies point to higher leptin levels associated with hypertension in humans, and animal data now convincingly suggest that leptin has direct central effects that increase sympathetic outflow to the kidneys, associated with increases in blood pressure. Although understanding of the pathophysiology of obesity-associated hypertension has made substantial progress during the past years, treatment of obese hypertensives remains largely empirical and clearly deserves to be addressed in larger randomized, controlled trials.