Acute vascular effects of vascular endothelial growth factor inhibition in the forearm arterial circulation. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Cameron, Alan C.; Welsh, Paul; Neves, Karla B.; Newby, David E.; Touyz, Rhian M.; Lang, Ninian N.
• Is Part Of: Journal of hypertension. Volume 38:Issue 2(2020:Feb.)
• Publication Date: 2020-02
• Subjects: bevacizumab -- endogenous fibrinolysis -- endothelin-1 -- endothelium-dependent vasodilatation -- forearm arterial vasomotor function -- hypertension -- neoangiogenesis -- vascular endothelial growth factor inhibitor; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000002230
• Languages: English
• ISSNs: 1473-5598

Abstract

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.