Elevated total body noradrenaline spillover in normotensive members of hypertensive families

In prehypertension, abnormalities in cardiovascular control mechanisms have been described. It has been postulated that this may involve hereditary disturbances in the sympathetic regulation of blood pressure. Since the neurochemical methods used to test sympathetic nervous system activity have been rather imprecise, in the present study we have applied noradrenaline plasma kinetic methodology to evaluate sympathetic activity in normotensive subjects with a familial predisposition to essential hypertension. Total body noradrenaline spillover to plasma, an index of integrated sympathetic nerve firing rates, was calculated during infusion of l-[7-3H] noradrenaline in 11 normotensive offspring of essential hypertensive parents and 11 age-, height- and weight-matched normotensive offspring of normotensive parents. The resting arterial plasma noradrenaline concentration was higher in healthy subjects with a family history of essential hypertension (1.41 ± 0.15 nmol/l, mean ± SEM, P < 0.002) than in normotensive subjects with no family history of essential hypertension (0.82 ± 0.07 nmol/l). The overall rate of spillover of noradrenaline to plasma was also elevated in the normotensive offspring of hypertensive parents (4.34 ± 0.54 nmol/min) compared with subjects with a negative family history of essential hypertension (2.02 ± 0.20 nmol/min). Similarly, the arterial plasma concentration of the noradrenaline precursor 3,4-dihydroxyphenylalanine was higher in subjects with a positive family history of essential hypertension (7.55 ± 0.24 nmol/l) than in normotensive control subjects (5.97 ± 0.30 nmol/l, P < 0.001). Despite this apparent evidence of relative sympathetic nervous activation in the subjects with a positive family history of hypertension, their blood pressure and heart rate were only marginally, and nonsignificantly, higher. Biochemical indices of thetic function in normotensive offspring of hypertensive parents suggest a familial disturbance in sympathetic nervous system activity, which may be a predictor for the development of hypertension in adult life.