An experimental study of VEGF induced changes in vasoactivity in pig retinal arterioles and the influence of an anti-VEGF agent

An isolated perfused retinal arteriole preparation was used. The outer diameter of retinal vessels was monitored at 2？second intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of intraluminal delivery of VEGF was determined over a wide concentration range (10-16 to 10-7 M) both with and without pre-contraction with ET-1 (3 x 10-9 M). Bevacizumab (0.35 mg mL-1) was applied extraluminally to determine the influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre-contracted vessels.In retinal arterioles with normal tone, VEGF induced a concentration dependent contraction at low concentrations, reaching 93.5% at 10-11 M and then contraction was reduced at higher concentrations, recovering to 98.1% at 10-7 M. VEGF produced a potent concentration dependent vasodilatation in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles pre-contracted with ET-1 was significantly inhibited by bevacizumab.VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles.Vascular endothelial growth factor (VEGF) is a protein with a high specificity for endothelial cells. In addition to its role in angiogenesis, VEGF also serves multiple important functions including pro-angiogenesis [1], enhancement of vascular permeability [2], changing vascular tone [3-7], and promotion of cell survival [8], division [9], and differentiation [10].Neovascular ocular diseases represent a major cause of vision loss in diseases such as proliferative diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity and retinal vascular occlusions [11]. Elevated VEGF has been found in these diseases [12,13]. VEGF has been considered to be an important pathogenic factor as well as a therapeutic target in ocular neovascularisations and associated changes [14]. Given the introduction of therapeutic intervent