This study investigates the effect of hypercholesterolemia on vascular function in humans, specifically examining the vasodilatory responses of forearm resistance vessels. The study involved 11 normal subjects (serum LDL cholesterol = 111±7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211±9 mg/dl). Vascular reactivity was assessed using methacholine and nitroprusside infusions to measure endothelium-dependent and endothelium-independent vasodilation, respectively. Basal and reactive hyperemic forearm blood flow were measured, and vasoconstrictive responsiveness to phenylephrine was evaluated. The results showed that while basal and reactive hyperemic blood flow were comparable between the two groups, the maximal forearm blood flow response to methacholine and nitroprusside was significantly blunted in hypercholesterolemic subjects. This suggests that hypercholesterolemia impairs the vasodilator responses to both endothelium-derived and exogenous nitrovasodilators, indicating a dysfunction in vascular smooth muscle or endothelium. The study concludes that hypercholesterolemia, even in the absence of atherosclerosis, can lead to impaired smooth muscle vasorelaxation, potentially contributing to vascular dysfunction and atherosclerosis.This study investigates the effect of hypercholesterolemia on vascular function in humans, specifically examining the vasodilatory responses of forearm resistance vessels. The study involved 11 normal subjects (serum LDL cholesterol = 111±7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211±9 mg/dl). Vascular reactivity was assessed using methacholine and nitroprusside infusions to measure endothelium-dependent and endothelium-independent vasodilation, respectively. Basal and reactive hyperemic forearm blood flow were measured, and vasoconstrictive responsiveness to phenylephrine was evaluated. The results showed that while basal and reactive hyperemic blood flow were comparable between the two groups, the maximal forearm blood flow response to methacholine and nitroprusside was significantly blunted in hypercholesterolemic subjects. This suggests that hypercholesterolemia impairs the vasodilator responses to both endothelium-derived and exogenous nitrovasodilators, indicating a dysfunction in vascular smooth muscle or endothelium. The study concludes that hypercholesterolemia, even in the absence of atherosclerosis, can lead to impaired smooth muscle vasorelaxation, potentially contributing to vascular dysfunction and atherosclerosis.