Acute vascular effects of vascular endothelial growth factor inhibition in the forearm arterial circulation

Cameron, A. C., Welsh, P. , Neves, K. B. , Newby, D., Touyz, R. M. and Lang, N. (2019) Acute vascular effects of vascular endothelial growth factor inhibition in the forearm arterial circulation. Journal of Hypertension, (doi:10.1097/HJH.0000000000002230) (PMID:31449168) (Early Online Publication)

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Abstract

Objective: Although vascular endothelial growth factor inhibition (VEGFi) represents a major therapeutic advance in oncology, it is associated with hypertension and adverse vascular thrombotic events. Our objective was to determine whether VEGFi caused direct vascular dysfunction through increased endothelin-1 (ET-1) activity or impaired endothelial vasomotor or fibrinolytic function. Methods: Using forearm venous occlusion plethysmography, we measured forearm blood flow during intra-arterial infusions of bevacizumab (36–144 μg/dl forearm volume per minute) administered for 15–60 min in healthy volunteers (n = 6–8). On two separate occasions in 10 healthy volunteers, we further measured forearm blood flow and tissue plasminogen activator (t-PA) release during intra-arterial bradykinin infusion (100 and 1000 pmol/min) in the presence and absence of bevacizumab (144 μg/dl forearm volume per minute), and the presence and absence of endothelin A receptor antagonism with BQ-123 (10 nmol/min). Plasma t-PA and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured at baseline and with each dose of bradykinin. Results: Baseline blood flow and plasma ET-1, t-PA and PAI-1 concentrations were unaffected by bevacizumab. Bradykinin caused dose-dependent vasodilatation (P < 0.0001) and t-PA release (P < 0.01) but had no effect on plasma PAI-1 concentrations. Neither bevacizumab nor BQ-123 affected bradykinin-induced vasodilatation and t-PA release. Conclusion: Acute exposure to bevacizumab does not directly cause endothelial vasomotor or fibrinolytic dysfunction in healthy young volunteers.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian and Newby, Professor David and Cameron, Dr Alan and Welsh, Dr Paul and Touyz, Professor Rhian and Neves, Dr Karla
Authors: Cameron, A. C., Welsh, P., Neves, K. B., Newby, D., Touyz, R. M., and Lang, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Hypertension
Publisher:Lippincott, Williams and Wilkins
ISSN:0263-6352
ISSN (Online):1473-5598
Published Online:19 August 2019
Copyright Holders:Copyright © 2019 Wolters Kluwer Health, Inc.
First Published:First published in Journal of Hypertension 2019
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
730981Cancer Chemotherapeutics and the Vasculature - Endothelial Effects of VEGF Inhibitorsion In Vivo in ManNinian LangChief Scientist office (CSO)TCS_16_31RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES