This paper provides a personal perspective of the role of abnormal renal-pressure natriuresis in the pathogenesis of hypertension. Direct support for a major role of renal-pressure natriuresis in long-term control of arterial pressure and sodium balance comes from studies demonstrating that (1) pressure natriuresis is impaired in all forms of chronic hypertension and (2) prevention of pressure natriuresis from operating, by servo-control of renal perfusion pressure, also prevents the maintenance of sodium balance hypertension. Although the precise mechanisms of impaired pressure natriuresis in essential hypertension have remained elusive, recent evidence suggests that obesity and overweight may play a major role. Obesity increases renal sodium reabsorption and impairs pressure natriuresis by activation of the renin-angiotensin and sympathetic nervous systems and by altered intrarenal physical forces. Chronic obesity also causes marked structural changes in the kidneys that eventually lead to a loss of nephron function, further increases in arterial pressure, and severe renal injury in some cases. Although there are many unanswered questions about the mechanisms of obesity hypertension and renal disease, this is one of the most promising areas for future research, especially in view of the growing, worldwide "epidemic" of obesity.
