Renal effects of hyperinsulinaemia in subjects with two hypertensive parents

The aim of this investigation was to study the effects of isoglycaemic hyperinsulinaemia on the renal metabolism of electrolytes and water in subjects with a strong genetic predisposition to essential hypertension, compared with that in non-predisposed subjects. We studied 25 normotensive subjects aged 18–35 years whose parents both had essential hypertension, and 22 age- and sex-matched subjects whose parents were both normotensive. Diabetes or morbid obesity in any subject or parent excluded the family. The 24-h blood pressure was measured. The subjects received an isocaloric diet with a fixed content of sodium and potassium for 4 days before the study. An isoglycaemic, hyperinsulinaemic clamp with infusion of insulin (40 munits·min^-1·m^-2) was performed. We measured the renal clearance of diethylenetriaminepenta-acetic acid, sodium, potassium and lithium both under basal conditions and during hyperinsulinaemia. In response to hyperinsulinaemia, renal sodium clearance decreased to a significantly greater extent in the hypertension-prone subjects [0.57 (0.74, 0.36) ml·min^-1·1.73 m² (median and quartiles)] than in the controls [0.34 (0.56, 0.18) ml·min^-1·1.73 m²] (P = 0.04). Compared with the controls, the subjects predisposed to hypertension had a higher 24-h diastolic blood pressure [78 (70, 82) mmHg, compared with 73 (68, 77) mmHg], but a similar insulin sensitivity index {10⁷×[313 (225, 427)] compared with 10⁷×[354 (218, 435)] l²·min^-1·pmol^-1·kg^-1}. Thus the sodium-retaining effect of insulin was more pronounced in subjects with a strong genetic predisposition to essential hypertension than in subjects with normotensive parents. This effect may contribute to the development of hypertension in subjects with a genetic predisposition to hypertension.