Role of Endogenous Vascular Endothelial Growth Factor in Endothelium-Dependent Vasodilation in Humans

Angiogenesis inhibitors have remarkably improved the outcome of patients with several types of cancer. Hypertension is the most reported side effect of angiogenesis inhibitors interfering with vascular endothelial growth factor signaling. In this study, we test the hypothesis that circulating vascular endothelial growth factor at physiological concentrations is essential to preserve normal endothelial control of vasomotor tone. In 7 healthy male volunteers, infusion of bevacizumab (monoclonal vascular endothelial growth factor antibody) into the brachial artery for 15 minutes (144 μg/dL forearm volume per minute) did not affect forearm vasodilator tone as measured with venous occlusion strain gauge plethysmography. In a separate group of 12 male volunteers, a similar bevacizumab infusion reduced the vasodilator response to 2 dosages of acetylcholine from (mean±SE) 440±157% and 926±252% to 169±40% and 612±154% (P