Louis K. Dahl Memorial Lecture. Renal and cardiovascular mechanisms of hypertension in obesity.

Abstract

In all forms of hypertension, including human essential hypertension, pressure natriuresis is reset to higher blood pressures. Because human essential hypertension is a heterogeneous disease, it is likely that there are multiple neurohumoral and intrarenal causes of abnormal pressure natriuresis and increased blood pressure. Weight gain is recognized to be an important contributor to essential hypertension, although the mechanisms that link obesity with altered renal function and high blood pressure have not been fully elucidated. In obese dogs and humans, the shift of pressure natriuresis to higher blood pressures appears to be due mainly to increased tubular reabsorption, as glomerular filtration rate and renal plasma flow are increased compared with normal. Multiple causes of increased tubular reabsorption and hypertension in obesity have been postulated, including insulin resistance and hyperinsulinemia, activation of the sympathetic nervous and renin-angiotensin systems, and physical changes within the kidney itself. Support for the insulin resistance-hyperinsulinemia link between obesity and hypertension has been inferred mainly from acute and epidemiologic studies showing a correlation between insulin and blood pressure. Recent studies suggest that chronic hyperinsulinemia, comparable to that found in obesity, cannot account for obesity hypertension in dogs or humans. Activation of the sympathetic nervous system may play a role in obesity-induced hypertension, and there is evidence for a role of altered intrarenal physical forces caused by histological changes within the renal medulla. The quantitative importance of each of these abnormalities in altering renal function and raising blood pressure in obesity remains to be determined but is an important area of research for understanding human essential hypertension.