Hyperinsulinemia and insulin resistance have been extensively reported in adult patients with essential hypertension. The aim of this study was to examine serum glucose and insulin levels both in the fasting state and after 0.25 g/kg IV glucose and to relate those findings to the status of intracellular Na + and red blood cell Na + -Li + countertransport in a population of 21 normolipemic normotensive offspring of hypertensive parents (N-EH) and 13 control children without a history of parental essential hypertension or diabetes mellitus matched for age, body mass index, and pubertal stage. Offspring of hypertensive parents presented significantly higher serum insulin levels both after an overnight fast (17.4±1.6 versus 11.6±1.6 fiU/mh in control [mean±SEM], P<.01) and after intravenous glucose than control subjects (insulin area under the curve, 3015±310 and 2057±234 jiU/mL per hour, respectively, P<.01). No relation could be established between the high red blood cell Na + -Li + countertransport (343±22 versus 215±15 /unol/L per hour, N-EH versus control; P<.002) or high intracellular Na + (9.8±0.28 versus 8.7 ±0.36 mEq/L, N-EH versus control) and hyperinsulinemia found in children of hypertensive parents. We conclude that the time precedence of hyperinsulinemia (and possibly insulin resistance) over the appearance of clinical hypertension in a high-risk population further supports the contention that an abnormal insulin action may play a pathogenetic role in essential hypertension. The lack of relation between hyperinsulinemia and red blood cell Na + -Li + countertransport or intracellular Na + suggests that either they are not linked in the causal pathway of hypertension or they are both an untimely product of a third yet undetermined pathogenetic factor.

Renal functional reserve, microalbuminuria, and plasma atrial natriuretic factor were measured in 21 offspring (9.5 +/- 0.5 years of age, mean +/- SEM) of hypertensive parents and in eight children (10 +/- 0.5 years of age) with no family history of hypertension who were used as a control group. Renal functional reserve was evaluated by measurement of the changes in creatinine clearance after an oral protein load of 45 g/m2. Atrial natriuretic factor levels were determined before and 60 minutes after the protein load, and microalbuminuria in fractional urine before and 120 minutes after the same stimulus as well as in a 24-hour urine collection. All children in the control group significantly increased their creatinine clearance after the protein load (preload, 122 +/- 12; 60 minutes, 144 +/- 9; 120 minutes, 154 +/- 11; 180 minutes, 144 +/- 9 ml/min/1.73 m2; all values were significant vs. preload, p less than 0.005). In contrast, only 13 of 21 offspring of hypertensive parents increased their creatinine clearance to values within 2 SD of the increase shown by the control group (preload, 144 +/- 11; 60 minutes, 153 +/- 7; 120 minutes, 202 +/- 13 ml/min/1.73 m2; p less than 0.001 vs. preload; 180 minutes, 214 +/- 19 ml/min/1.73 m2, p less than 0.001 vs. preload). The remaining eight offspring of hypertensive parents showed no detectable changes (nonresponders) (preload, 189 +/- 18; 60 minutes, 146 +/- 11; 120 minutes, 170 +/- 14; 180 minutes, 168 +/- 13 ml/min/1.73 m2; all values p = NS). No changes in atrial natriuretic factor after the protein load were observed in any group. Offspring of hypertensive parents presented higher microalbuminuria levels in 24-hour urine specimens (3.1 micrograms/min, tolerance factor [TF]2.2) than controls (2.1 micrograms/min, TF 1.5) (p less than 0.05). Although microalbuminuria increased significantly after the water load in the control group (p less than 0.05) and in the offspring of hypertensive parents (p less than 0.01), it returned to baseline at 120 minutes in the former but not in the latter (p less than 0.05 vs. baseline). The lack of renal functional reserve in nonresponders was significantly related (p less than 0.05) to the presence of higher levels of microalbuminuria. We conclude that the absence of renal functional reserve and increased microalbuminuria in some normotensive children who are offspring of essential hypertensive parents can indicate that subtle alterations in renal function may precede the onset of clinical hypertension.

Family history of hypertension and obesity are both risk factors for hypertension. Hypertension and obesity share several physiopathologic abnormalities and are frequently associated. However, not all obese people are hypertensive. Renal handling of sodium has been proposed as a physiopathogenic mechanism of essential hypertension and obesity. This study was conducted in obese adolescents to evaluate the role of a family history of hypertension versus obesity in the renal handling of sodium. .5% ؎ 1.3%, in ON it was 22.4% ؎ 2.3%, and in LH it was 14.4% ؎ 1.2% (P < .05). FEUA in OH was 8.5% ؎ 0.8%, in ON it was 14.8% ؎ 3.6%, and in LH it was 7.9% ؎ 0.8% (P < .01). Plasma renin activity (PRA) and aldosterone (PA) were measured in OH and LH; PRA was 5.3 ؎ 0.4 and 4.5 ؎ 0.4 ng/mL/h, respectively (P ‫؍‬ NS), and PA was 366 ؎ 36 and 242 ؎ 32 pg/mL, respectively (P < .05). In summary, adolescents with a family history of hypertension, regardless of their body mass, have a diminished FELi and FEUA. Obese adolescents also have higher plasma levels of aldosterone than lean ones. In conclusion, the family history of hypertension would be related to the increased renal proximal sodium reabsorption whereas obesity would be related to increased distal sodium reabsorption mechanisms, such as aldosterone. Both mechanisms could explain the higher prevalence of hypertension in obese offspring of hypertensive parents. Am J Hypertens 1999;12:260 -263

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We previously showed that children and adolescent offspring of patients with essential hypertension have an increased proximal renal sodium reabsorption as measured by lithium fractional excretion. Insulin has been shown to have antinatriuretic properties and to be increased (hyperinsulinemia) in essential hypertension. The aim of this study was to evaluate the role of insulin on the increased proximal renal sodium reabsorption previously reported. Lithium and sodium fractional excretions were measured 3 hours before and 3 hours after an intravenous glucose tolerance test in 20 normotensive adolescents with a family history of essential hypertension (F+, 14.8 +/- 0.5 years) and 10 normotensive control subjects without a family history of hypertension (F-, 15.2 +/- 0.9 years). Results are mean +/- SEM. Lithium fractional excretion before glucose loading was 16.1 +/- 1.8% in F+ versus 23.5 +/- 2.0% in F- (P < .02) and after glucose loading was 14.7 +/- 1.3% in F+ versus 20.9 +/- 1.7% in F- (P = NS). Lithium fractional excretion did not change after intravenous glucose loading in either group. The insulin area under the curve was 2815 +/- 499 in F+ versus 2290 +/- 418 microU/mL per hour in F- (P = NS). There was no correlation between lithium fractional excretion and insulin area under the curve. Fractional excretion of sodium before glucose loading was 0.99 +/- 0.1% in F+ versus 0.99 +/- 0.1% in F- (P = NS) and after glucose loading was 0.77 +/- 0.1 in F+ versus 0.85 + 0.1% in F- (P < .01 versus values before loading in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)