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


METHODS
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.


RESULTS
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.


CONCLUSIONS
VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles.
Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
Er-Ning
EN
Su
Stephen J
SJ
Cringle
Ian L
IL
McAllister
Dao-Yi
DY
Yu
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000502:physiology; D000068258:Bevacizumab / Q000494:pharmacology*; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D019332:Endothelin-1 / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D012161:Retinal Artery / Q000502:physiology*; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D019332:Endothelin-1; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab