Angiogenesis inhibitors have remarkably improved treatment of patients with several types of cancer. One of the most reported side effects of angiogenesis inhibitors is hypertension. In patients treated with bevacizumab, a monoclonal antibody against vascular endothelial growth factor, hypertension had an overall incidence up to 32%. The increase in blood pressure occurs early in treatment. Understanding the pathogenesis of this side effect is essential for optimal treatment with this class of drugs. One of the main targets of angiogenesis-inhibitors is the vascular endothelial growth factor and its receptors. Animal and human studies show that VEGF induces vasodilatation and hypotension by stimulation of NO production. Moreover animal studies suggest that endogenous VEGF may play a role in maintaining normal vascular tone in blood vessels. Theoretically, inhibition of the VEGF-pathway in humans would decrease NO production causing vasoconstriction and thereby induce hypertension. Intra-arterial bevacizumab infusion causes acute local vasoconstriction.

Methods: In 7 healthy male volunteers the acute vasomotor effect of bevacizumab was studied. During 15 minutes bevacizumab 144 mg/dl forearm volume/min was infused in the brachial artery of the non-dominant arm while assessing forearm blood flow with plethysmography. The dosage was calculated to reach a local concentration of 120 mg/l. resembling therapeutic concentrations. During bevacizumab infusion venous blood was collected from both arms to measure local and systemic concentrations of bevacizumab. Intra-arterial infusion of bevacuzimab did not significantly alter vascular tone expressed as vascular resistance or flow ratio. Intra-arterial bevacizumab was well tolerated. Intra-arterial Bevacizumab (144 mg/dl forearm volume/min for15 minutes) does not increase muscle vascular tone as a potential mechanism of hypertension.