Purpose: Angiotensin II (ANG) is implicated in the development of cardiovascular disease. We examined vascular responses to ANG in subjects with familial hypercholesterolemia (FH), a group at high cardiovascular risk.

Methods: The effects of ANG (3h iv infusion, 10 g/kg/min) on brachial blood pressure and forearm skin microvascular function were studied in 8 female and 8 male FH (mean age 43±8 ys) and in 16 matched healthy controls. Skin microcirculation was studied by laser Doppler fluxmetry during rest and local heating of the skin to 44°C (microvascular hyperaemia). Microvascular resistance was assessed by mean arterial pressure/microvascular hyperaemia, and macrovascular reactivity by blood pressure changes. Measurements were performed before, at 1 and 3h of ANG, and 1h after stopping infusion. Mean values ±SD.

Results: Baseline systolic blood pressure was higher in FH (127±14 vs 115±12 mm Hg; p=0.02), while pressure responses to ANG were similar in both groups (eg +24±10 vs +21±7 mm Hg, ANG 3 h). There were no baseline differences in microvascular hyperaemia or resistance between the groups. However, during and after ANG microvascular hyperaemia was impaired (p=0.01; eg 126±95 vs 184±102 units, ANG 3 h), and microvascular resistance higher (p=0.01; eg 1.9±0.9 vs 0.9±0.8 mm Hg/units; ANG, 3 h) in FH. Saline infusion verified stability of the experimental design (n=8).

Conclusions: Despite similar blood pressure responses to ANG in FH and controls, microvascular dilatation capacity was impaired in FH, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and cardiovascular complications in FH.