Family history of essential hypertension versus obesity as risk factors for hypertension in adolescents.

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. Fractional excretion of lithium (FELi) and uric acid (FEUA) were measured in 46 obese adolescent offspring of hypertensive parents (OH: body mass index [BMI], 29.5 +/- 0.6 kg/m2, age 14.2 +/- 0.3 years, 22 males); eight obese offspring of normotensive parents (ON: BMI, 30.7 +/- 1.7 kg/m2, 14.8 +/- 0.8 years, four males), and in 34 lean adolescent offspring of hypertensive parents (LH: BMI, 20.5 +/- 0.5 kg/m2, 14.3 +/- 0.3 years, 24 males). FELi in OH was 16.5% +/- 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.

Calcium-ATPase and insulin in adolescent offspring of essential hypertensive parents.

A number of abnormalities in calcium homeostasis have been reported in patients with essential hypertension. IN turn, insulin has been shown to influence the activity of the Ca(2+)-ATPase. We have previously shown that normotensive offspring of essential hypertensive individuals have an exaggerated insulin response to a glucose overload. Therefore, the aim of the present study was to evaluate basal and calmodulin-activated Ca(2+)-ATPase in red blood cells and its relationship to the insulin response during an intravenous glucose tolerance test in 27 normotensive adolescents with a family history of essential hypertension (F+) (mean age, 13.9 +/- 0.5 years) and in 10 control subjects matched for age and body mass index with no family history of hypertension (F-). The results (mean +/- SD) were as follows (mumol Pi/[mg protein/h]10(-1)): basal Ca(2+)-ATPase, 4.5 +/- 1.2 in F+ and 5.1 +/- 1.6 in F- (P = NS); calmodulin-activated Ca(2+)-ATPase, 13.6 +/- 3.9 in F+ and 16.2 +/- 1.7 in F- (P < .04). The insulin area under the curve after the glucose load was 3413 +/- 1674 microU/mL per hour in F+ and 2752 +/- 928 in F- (P = NS). Calmodulin-activated Ca(2+)-ATPase showed a negative correlation with the insulin area under the curve (r = -.59, P < .005) and cholesterol levels (r = -.38, P < .03). Urinary calcium excretion was 1.82 +/- 0.9 mmol/d in F+ and 2.47 +/- 0.9 mmol/d in F- (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin effect on renal sodium reabsorption in adolescent offspring of essential hypertensive parents.

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)

Renal functional reserve compared in haemolytic uraemic syndrome and single kidney.

Creatinine clearance and microalbuminuria were measured before and after an oral protein load in 17 children with a history of haemolytic uraemic syndrome, 11 with a single kidney, and 15 controls, all of them normotensive and without evidence of renal damage, to look for indirect evidence of glomerular hyperfiltration. While creatinine clearance increased significantly after the protein load in controls, it did not change in patients with either haemolytic uraemic syndrome or a single kidney. Basal microalbuminuria was significantly higher in those with haemolytic uraemic syndrome when compared with those with a single kidney and controls. It increased significantly in all groups after a water load; this increase was significantly higher in haemolytic uraemic syndrome. After the protein load microalbuminuria returned to baseline. In conclusion, children with a history of haemolytic uraemic syndrome have an abnormal renal functional reserve like children with a single kidney. Only patients with haemolytic uraemic syndrome exhibited an increased microalbuminuria, however, suggesting that it may be the expression of a pathophysiological mechanism involved in haemolytic uraemic syndrome and not in single kidney, that could account for their different prognosis.

Renal functional reserve and microalbuminuria in offspring of hypertensive parents.

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.

[Sodium transport in red blood cell membranes in essential arterial hypertension]. / Transporte de sodio en membrana de glóbulos rojos en hipertensión arterial esencial.

Several abnormalities in Na metabolism have been implicated in the pathogenesis of essential hypertension. In addition, recent work by several investigators has showed that some Na transport systems in red cell membranes may be altered in those patients. In order to confirm such abnormalities we evaluated simultaneously four different and clearly defined Na transport systems in red cell membranes: the ouabain sensitive Na pump (P) and the Na-K cotransport (Co) in nystatin loaded cells, the maximal rate of Na-Li countertransport (CTT) in lithium loaded cells and the rate constant of Na passive permeability (pp) in 58 normotensive control subjects with no family history of hypertension (N), 19 normotensive subjects with family history of hypertension (NH) and 34 essential hypertensive patients (HE). The mean (mean +/- SEM microns/lc/h) value of the P and pp was found to be comparable in the three groups. Co was found significantly decreased in both HE (241 +/- 28) and in NH (227 +/- 42) when compared to the control group (290 +/- 10). Although NH also showed CTT values (377 +/- 87) higher than controls, the difference did not reach statistical significance. Our results indicate that approximately 90.9% of both HE and NH presented abnormalities in one or more of the various Na transport systems studied. Normotensive patients with a positive family history and alterations in some of the Na transport systems in red cell membranes may prove an interesting experimental model to assess the importance of such alterations for the development of hypertension.

Transporte de sodio en membrana de glóbulos rojos en hipertensión arterial esencial. / [Sodium transport in red blood cell membranes in essential arterial hypertension]

Several abnormalities in Na metabolism have been implicated in the pathogenesis of essential hypertension. In addition, recent work by several investigators has showed that some Na transport systems in red cell membranes may be altered in those patients. In order to confirm such abnormalities we evaluated simultaneously four different and clearly defined Na transport systems in red cell membranes: the ouabain sensitive Na pump (P) and the Na-K cotransport (Co) in nystatin loaded cells, the maximal rate of Na-Li countertransport (CTT) in lithium loaded cells and the rate constant of Na passive permeability (pp) in 58 normotensive control subjects with no family history of hypertension (N), 19 normotensive subjects with family history of hypertension (NH) and 34 essential hypertensive patients (HE). The mean (mean +/- SEM microns/lc/h) value of the P and pp was found to be comparable in the three groups. Co was found significantly decreased in both HE (241 +/- 28) and in NH (227 +/- 42) when compared to the control group (290 +/- 10). Although NH also showed CTT values (377 +/- 87) higher than controls, the difference did not reach statistical significance. Our results indicate that approximately 90.9

of both HE and NH presented abnormalities in one or more of the various Na transport systems studied. Normotensive patients with a positive family history and alterations in some of the Na transport systems in red cell membranes may prove an interesting experimental model to assess the importance of such alterations for the development of hypertension.

Long-term systemic hypertension in children after successful repair of coarctation of the aorta.

The mechanisms responsible for long-term hypertension in children after successful repair of coarctation of the aorta have not yet been determined. We measured plasma renin activity and aldosterone, adrenalin, and noradrenalin concentrations both under basal conditions and in response to standing and treadmill exercise in 24 normal normotensive children, 16 normotensive postcoarctectomy children, eight hypertensive postcoarctectomy children, and seven children with essential hypertension. Exercise-induced changes in plasma renin activity, aldosterone, adrenalin, and noradrenalin were comparable in the four groups in spite of a significantly greater increase in systolic blood pressure in the children with hypertension. In response to standing, the plasma concentration of noradrenalin increased significantly in normotensive but not in hypertensive children. Hyperresponse of blood pressure to exercise in hypertensive postcoarctectomy children and children with essential hypertension is not related to abnormalities in the sympathetic nervous system or the angiotensin-aldosterone axis. Hypertension could be related to primary baroreceptor alterations, to structural changes in the arterial wall, or both. Twenty percent of normotensive postcoarctectomy children had a blood pressure hyperresponse to exercise and an abnormal noradrenalin response to standing similar to that seen in the hypertensive children. Follow-up of children after coarctectomy may elucidate whether these two abnormalities are indicators of an increased risk of developing long-term recurrent hypertension.