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

Abstract

BackgroundVascular endothelial growth factor (VEGF) plays an important role in ocular physiology. Anti-VEGF agents are now used for treatment of common retinal diseases. This study characterises the vasoactive properties of VEGF in isolated perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1) pre-contracted conditions and determines the influence of an anti VEGF agent on VEGF induced vasoactivity.MethodsAn 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.ResultsIn 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.ConclusionsVEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles.

Deterioration of Retinal Blood Flow Parameters in Branch Retinal Vein Occlusion Measured by Doppler Optical Coherence Tomography Flowmeter

“…Here, the number of anti-VEGF injections was not significantly correlated with the diameter of the occluded vein in the BRVO eye (Table 3). VEGF has a vasodilatory effect, and previous reports have suggested that anti-VEGF can be used to suppress the vasodilatory effect and reduce the permeability of the blood vessel [19]. However, in the current study, there was no significant correlation between the number of anti-VEGF injections and vessel diameter, suggesting that anti-VEGF treatment does not suppress vasodilation over long periods.…”

VEGF can protect against blood brain barrier dysfunction, dendritic spine loss and spatial memory impairment in an experimental model of diabetes

“…It is conceivable that if VEGF serves to regulate vascular tone (Bardal et al, 2006) or BBB integrity, a chronic deficiency in VEGF signaling in the diabetic hippocampus could lead to an increase in the number of dilated vessels. This idea is supported by a recent study where local application of VEGF led to constriction of isolated retinal arterioles (Su et al, 2012). Alternatively, since diabetes has been linked to changes in cerebral perfusion in some reports (Harik and LaManna, 1988;Knudsen et al, 1991;Manschot et al, 2003;Wu et al, 2008) but not others (Jakobsen et al, 1990), vessel dilation could be a compensatory mechanism for maintaining sufficient blood flow to meet the high metabolic demands of the hippocampus (Stranahan and Mattson, 2008).…”

Bevacizumab-induced hypertension: Clinical presentation and molecular understanding

“…Direct administration of VEGF has been shown to induce vasorelaxation and lower BP (Henry et al, 2003; 2001; Horowitz et al, 1997). Bevacizumab inhibited VEGF-induced vasodilation, measured by outer vessel diameter, in pig retinal arterioles (Su, Cringle, McAllister, & Yu, 2012), and local administration of bevacizumab in human subjects rapidly decreased endothelium-dependent vasodilation (Thijs et al, 2013). Thus, inhibition of VEGF signaling and decreased endothelium-dependent vasodilation may result in overall vascular resistance and the development of HTN.…”