ObjectiveAn increased sensitivity to angiotensin II (Ang II) has been observed in patients with established hypertension. In the current study we tested whether young normotensive subjects with positive family history of arterial hypertension exhibit an increased sensitivity to Ang II, thereby potentially contributing to the pathogenesis of essential hypertension in these subjects.Methods and designNormotensive young men (25±2 years) with positive family history (PFH) (n= 28) and negative family history (NFH) (n= 60) of arterial hypertension were investigated to study aldosterone response, and systemic and renal haemodynamic changes (p-aminohippurate- and inulin-clearance) to Ang II infusion (0.5 and 3.0 ng/min per kg). In addition, aldosterone response to salt loading (5 g/day for 1 week) was analysed.ResultsAmbulatory blood pressure (ABP) (mean: 84±4 versus 83±4 mmHg; NS), body mass index (23.5±2.5 versus 24.1±2.4 kg/m2; NS), and urinary sodium excretion (191±55 versus 170±73 mmol/24 h; NS) did not differ between PFH and NFH at baseline. Changes in BP, urinary sodium and potassium excretion were similar between PFH and NFH in response to salt loading. However, salt loading did not result in an adequate suppression of aldosterone in PFH compared with NFH (8±62 versus −32±39 pg/ml;P<0.001). Baseline values and changes in mean arterial BP (NFH: +13.4±7.6; PFH: +14.4±5.3 mmHg; NS), renal plasma flow (NFH: – 113±68; PFH: – 122±64 ml/min; NS) and glomerular filtration rate (NFH: +5.0±5.3; PFH: +4.2±8.3 ml/min; NS) in response to Ang II (3.0 ng/min per kg) were similar between the two groups. In contrast, the increases in serum aldosterone (PFH: 63.6±70.1 versus NFH: 37.7±46.8 pg/ml;P<0.05) and urinary potassium excretion (PFH: 0.05±0.1 versus NFH: −0.01±0.07 mmol/min;P<0.05) 30 min after stopping Ang II infusion were more pronounced and prolonged in PFH than in NFH.ConclusionsOur findings suggest that young normotensive subjects with parental history of arterial hypertension are characterized by an inadequate suppression of aldosterone production in response to salt loading and an exaggerated and prolonged hyper-responsiveness of aldosterone secretion in response to Ang II. This might contribute to the increased risk for the development of essential hypertension in subjects with positive family history of arterial hypertension.