|Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation.|
|PMID: 18056916 Owner: NLM Status: MEDLINE|
|Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP). We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.|
|J-J Mourad; G des Guetz; H Debbabi; B I Levy|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-04|
|Title: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO Volume: 19 ISSN: 1569-8041 ISO Abbreviation: Ann. Oncol. Publication Date: 2008 May|
|Created Date: 2008-04-29 Completed Date: 2008-06-24 Revised Date: 2013-05-27|
Medline Journal Info:
|Nlm Unique ID: 9007735 Medline TA: Ann Oncol Country: England|
|Languages: eng Pagination: 927-34 Citation Subset: IM|
|Avicenne Hospital Assistance Publique-Hôpitaux de Paris, Paris XIII University (EA3412), Bobigny, France.|
|APA/MLA Format Download EndNote Download BibTex|
Angiogenesis Inhibitors / adverse effects*, pharmacology, therapeutic use
Antibodies, Monoclonal / adverse effects*, pharmacology, therapeutic use
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Blood Pressure / drug effects*
Capillaries / drug effects
Cholinergic Agents / administration & dosage, pharmacology
Colorectal Neoplasms / blood supply, drug therapy
Diabetes Mellitus, Type 2 / complications, physiopathology
Endothelium, Vascular / drug effects, physiopathology
Fingers / blood supply
Forearm / blood supply
Hypertension / chemically induced*
Microcirculation / drug effects*
Neovascularization, Pathologic / drug therapy*
Pilocarpine / administration & dosage, pharmacology
Vasodilation / drug effects
|0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Cholinergic Agents; 2S9ZZM9Q9V/bevacizumab; 92-13-7/Pilocarpine|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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