Mechanisms of Hypertension Associated with Obesity

Background. Obesity is extremely common in people with high BP. However, the mechanisms by which BP increases in obese subjects are unknown. Objectives. We are interested in understanding the role of dietary salt and the BP reactivity to dietary salt (salt sensitivity) in the genesis of hypertension associated with obesity. We have recently shown that individuals with the metabolic syndrome are more salt sensitive that those without the syndrome. In addition, we have reported that high salt intake is associated with indices of obesity (BMI, weight and waist circumference). However, not all obese individuals have high BP, nor weight loss lowers BP in all subjects. Methods and Results. Therefore, a prospective study was designed to investigate the role of the salt sensitive (SS) and the salt resistant (SR) phenotypes in determining the degree of BP lowering induced by weight loss. Overweight/obese classified as SS or SR (n=45; BMI:27-35 kg/m2) entered a 1-year program of dietary restriction, aerobic exercise and metformin. Comparable reductions in obesity (8-10%), triglyceride (25%), and fasting insulin concentrations (40%) were observed in SR and SS individuals. In SS subjects the intervention lowered SBP/DBP by 8.8/6.1 mmHg, albuminuria by 63%, and decreased the subject’s SS. Neither BP nor albuminuria was modified in SR by the intervention. However, in obese SS individuals, restricting dietary salt lowered BP to a similar extent to the BP reduction achieved with the one-year intervention (weight loss). Conclusions. Our findings indicate that BP lowering induced by the lifestyle-metformin intervention appears to be determined by the SR/SS phenotype. Correcting adiposity in SS lowers BP because it makes the BP insensitive to dietary salt (corrects the SS phenotype). Therefore, weight loss and correction of metabolic abnormalities lowers BP in obese SS but not in obese SR, suggesting that the SR phenotype protects from obesity-induced increases in BP. These findings suggest that most of the hypertension associated with obesity is determined by dietary salt intake due to the development of a SS phenotype. The mechanisms (genetic or acquired) that determine the SS phenotype are under investigation