Obesity, insulin resistance, and the renal circulation

Weight gain causes high blood pressure in many essential hypertensive patients, and may be a major cause of ESRD. Although the precise mechanisms by which obesity raises blood pressure have not been fully elucidated, weight gain is associated with increased renal tubular reabsorption of sodium and a shift of pressure natriuresis toward higher blood pressures. The increased renal tubular reabsorption is compensated for, in part, by renal vasodilation and glomerular hyperfiltration. However, chronic renal vasodilation also raises hydrostatic pressure and wall stress in the glomeruli which, along with activation of neurohumoral factors and increased lipids and glucose intolerance, may cause glomerulosclerosis and loss of nephron function in obese subjects. The mechanisms by which obesity increases tubular reabsorption and shifts pressure natriuresis toward higher blood pressures are not completely understood, but do not appear to be directly related to hyperinsulinemia. Activation of the sympathetic and renin-angiotensin systems, as well as changes in intrarenal physical forces caused by medullary compression, appear to play a key role in the pathogenesis of obesity hypertension. However, the mechanisms that initiate these changes remain a fruitful area for further investigation, especially in view of the importance of weight gain as a cause of human essential hypertension and ESRD.