To clarify the role of sodium intake in the regulation of blood pressure in obese subjects, we measured blood pressure in 60 obese and 18 nonobese adolescents after successive two-week periods of a high-salt diet (greater than 250 mmol of sodium per day) and a low-salt diet (less than 30 mmol per day). When they were changed from a high-salt to a low-salt diet, the obese group had a significantly larger mean change (+/- SE) in mean arterial pressure (-12 +/- 1 mm Hg) than did the nonobese group (+1 +/- 2 mm Hg; P less than 0.001). The variables that best predicted the degree of sodium sensitivity were the fasting plasma insulin level, the plasma aldosterone level while the low-salt diet was being given, the plasma norepinephrine level while the high-salt diet was being given, and the percentage of body weight made up by fat. Fifty-one of the obese adolescents were also studied before and after a 20-week weight-loss program. After the weight-loss program, the 36 subjects who lost more than 1 kg of body weight had a reduced sensitivity of blood pressure to sodium (difference from value during high-salt diet to that during low-salt diet, -1 +/- 1 mm Hg). The blood pressure of the remaining 15 adolescents was still sensitive to sodium intake (-11 +/- 3 mm Hg). These results support the hypothesis that the blood pressure of obese adolescents is sensitive to dietary sodium intake and that this sensitivity may be due to the combined effects of the hyperinsulinemia, hyperaldosteronism, and increased activity of the sympathetic nervous system that are characteristic of obesity.

The effect of insulin on the renal handling of sodium was studied in obese and nonobese subjects by using euglycemic hyperinsulinemia. Seven water-loaded obese (14-19 years old) and five nonobese young adults (18-21 years old) had insulin given intravenously at a rate of 40 munits/m 2 /min. Blood glucose and creatinine clearance were not altered by euglycemic hyperinsulinemia in either the obese or the nonobese group. Hyperinsulinemia resulted in a significant decrease in urinary sodium excretion in both groups of subjects (by 54.2±3% [mean±SEM] in the obese and by 50.9±3.1% in the nonobese group). However, the amount of glucose required to maintain euglycemia was significantly less in the obese versus nonobese group, 89.5±6.2 versus 329.2±16 mg glucose/m 2 /min (p<0.001). There was no relation in either group between the amount of glucose required to maintain euglycemia and the change in urinary sodium excretion. On a separate day, all of the obese subjects underwent 3 hours of water diuresis but without insulin. There was no change in urinary sodium excretion with sustained water diuresis alone. However, when compared with the nonobese group, the obese group of subjects had a significantly higher resting mean arterial pressure, heart rate, and plasma norepinephrine concentration; during the insulin clamp, neither group experienced a significant change in mean arterial pressure or heart rate, and only the nonobese group experienced an increase in plasma norepinephrine. In obese subjects, we have found, despite the presence of insulin resistance to carbohydrate metabolism, that euglycemic hyperinsulinemia was associated with a normal decrease in urinary sodium excretion. Therefore, the data support the hypothesis that insulin resistance with respect to glucose metabolism leads to hyperinsulinemia, which in turn could lead to chronic sodium retention. (Hypertension 1989;14:367-374) S tudies conducted on subjects with essential hypertension, 1 -2 obesity, 3 -5 or non-insulindependent diabetes mellitus 6 have demonstrated an association between hyperinsulinemia and hypertension. Numerous in vitro and in vivo studies have been published documenting that physiological changes in plasma insulin concentration are capable of altering electrolyte transport by the kidney.7 -12 Since obesity is associated with hyperinsulinemia and insulin resistance, it has been sug-

These data suggest that this novel transhepatic approach provides an effective and safe route for diagnostic and interventional cardiac catheterization in children.

To study the relationship between body weight and blood pressure, we have developed an animal model of obestiy-induced hypertension. Nine adult mongrel dogs were chronically instrumented with aortic and vena caval catheters. After a 2-week control period, all dogs were made to gain weight by adding 2 Ib/day of beef fat to their diet for 5 weeks. Blood pressure, heart rate, and body weight were measured daily before the addition of dietary fat, during the 5 weeks of the high fat diet, and for 6 weeks after the fat supplement was stopped. Plasma volume and cardiac output were measured prior to and after 5 weeks of the fat diet. During the 5-week high fat diet, the dogs' body weight increased from 22.2 ± 2.1 to 27.4 ± 3 kg (p<0.001); mean blood pressure increased from 90 ± 5 to 112 ± 6 mm Hg (p<0.01); and heart rate increased from 70 ± 7 to 85 ± 5 beats/min (p<0.05). Blood pressure, heart rate, and body weight returned to near control values after the fat diet was stopped. Over the 5-week fat diet, the dogs' plasma volume increased from 920 ± 130 to 1059 ± 195 ml (p<0.05); cardiac output increased from 2.5 ± 0.4 to 3.1 ± 0.3 L/min (p<0.05); and systemic vascular resistance increased from 35.3 ± 8 to 38.9 ± 9 mm Hg/L/min (p<0.1). Weight gain in the dogs was also associated with hyperinsulinemia and insulin resistance. Our findings have demonstrated that weight gain in the dog is associated with an increase in heart rate, blood pressure, cardiac output, plasma volume, and fasting insulin concentration, and we think that our animal model should be ideal for studying the pathogenesis of obesity-induced hypertension. (Hypertension 9 [Suppl III]: III-64-III-68, 1987) KEY WORDS • obesity • hypertension • hyperinsulinemia