Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats.

Journal article


Fretwell, Laurice, Woolard, Jeanette and Carter, Joanne 2016. Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. The FASEB Journal. https://doi.org/10.1096/fj.201600749R
AuthorsFretwell, Laurice, Woolard, Jeanette and Carter, Joanne
Abstract

VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms involved, we evaluated their regional hemodynamic effects in conscious rats. Male Sprague Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes (renal and mesenteric arteries, and the descending abdominal aorta) and catheters (jugular vein, peritoneal cavity, and distal abdominal aorta). Regional hemodynamics were measured over 4 d, before and after daily administration of cediranib (3 and 6 mg/kg, 3 and 6 mg/kg/h for 1 h, i.v.), sorafenib (10 and 20 mg/kg, 10 and 20 mg kg/h for 1 h, i.v.), pazopanib (30 and100 mg/kg, i.p.), or vandetanib (12.5 and 25 mg/kg, i.p.). All drugs evoked significant increases.

KeywordsCancer therapy; RKTI; VEGF; Hypertension; Regional haemodynamics
Year2016
JournalThe FASEB Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
PublisherFASEB
ISSN1530-6860
Digital Object Identifier (DOI)https://doi.org/10.1096/fj.201600749R
Web address (URL)http://hdl.handle.net/10545/623515
hdl:10545/623515
Publication dates16 Dec 2016
Publication process dates
Deposited21 Feb 2019, 16:27
Accepted03 Dec 2016
ContributorsDe Montfort University, Leicester and University of Nottingham
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