A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. Abstract: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. Design: In 43 hypertensive patients(HT) and 38 normotensive controls(NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation(FMD), using high-resolution ultrasound. Peripheral flow reserve(FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. Results: FMD was markedly impaired in HT(3.6± 0.3% ) as compared with NT(10.2± 0.3% ), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced(HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD(r=0.68, P< 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD(r2=0.46, P< 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60% . Conclusions: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.u001a A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit art. Both have been demonstrated to predict future cardiovascular events. Abstract: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. Design: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation ( Results: FMD was markedly impaired in HT (3.6 ± 0.3% ) as compared with NT (10.2 ± 0.3%), while maximum brachial artery diameter fol Lowing endothelium-independent dilatation was similar in all groups. FR was associated with FMD (r = 0.68, P <0.01) . Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P <0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. Conclusions: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream duct arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension. U001a