The effects of bevacizumab on rat abdominal aorta physiologic responses

Bevacizumab is a recombinant humanized monoclonal antibody which specifically binds to human vascular endothelial growth factor receptor. It inhibits the binding of vascular endothelial growth factor (VEGF) to its receptor and neutralize the vascularization of the tumor, thus slow the growth in cancer treatment. In cancer patients who had treated with bevacisumab, hypertension had been observed in amount of %34 patients. Available data suggest that the vascular endothelium as the main source of hypertension, there is no comprehensive study on this subject. This study investigated the in vitro effects of bevacizumab in the artery physiology. Bevacizumab was administered doses of 35 mg/kg to Wistar rats intravenously once every 21 days a total of 3 times. 7 days after the last application the rats were sacrificed, the abdominal aorta was removed and was hanged on the organ bath properly. Angiotensin II, norepinephrine and endothelin-1 with cumulatively concentrations and 30 mM KCl with a single concentration contractile responses, phenylephrine in front contractions generated preparations acetylcholine or sodium nitroprusside relaxant responses and L-arginine, NG-nitro-L-arginine methyl ester (L-NAME ), indomethacin acetylcholine concentration-response curves after incubation with L-NAME+indomethacin finally after incubation with indomethacin+charybdotoxin+apamin, bevacizumab were administered and were not administered to group, were obtained acetylcholine concentration response curves. There was no significant difference in blood pressure measured at the beginning and after 3 prior bevacizumab administration were observed in this study. Contraction responses were not found a significant differences compared to the control group. After the incubation of L-arginine, the response of vascular relaxation was increased and vascular relaxation had been observed statistically significant only induced by acetylcholine compared to control. Our results indicate that bevacizumab beyond vasoconstriction response impairs the response of relaxation. Our results suggest that hypertensive side effects during the treatment of drug are occured from the deterioration of the endothelium-derived NO generated / releasement.