Skip to main content

Research Repository

Advanced Search

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

Carter, Joanne J.; Fretwell, Laurice; Woolard, Jeanette

Authors

Joanne J. Carter

Laurice Fretwell

JEANETTE ISAAC Jeanette.Woolard@nottingham.ac.uk
Professor of Cardiovascular Physiology and Pharmacology



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 (P < 0.05; n = 7–8) in mean arterial pressure, which were generally accompanied by significant mesenteric and hindquarters, but not renal, vasoconstrictions. The hypertensive effects of cediranib were unaffected by losartan (10 mg/kg/h), bosentan (20 mg/kg/h), or a combination of phentolamine and propranolol (each 1 mg/kg/h), suggesting a need for new strategies to overcome them.—Carter, J. J., Fretwell, L. V., Woolard, J. Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats.

Citation

Carter, J. J., Fretwell, L., & Woolard, J. (2017). Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. FASEB Journal, 31(3), 1193-1203. https://doi.org/10.1096/fj.201600749r

Journal Article Type Article
Acceptance Date Dec 3, 2016
Online Publication Date Dec 16, 2016
Publication Date 2017-03
Deposit Date Jan 23, 2017
Publicly Available Date Jan 23, 2017
Journal FASEB Journal
Print ISSN 0892-6638
Electronic ISSN 1530-6860
Publisher Federation of American Society of Experimental Biology
Peer Reviewed Peer Reviewed
Volume 31
Issue 3
Pages 1193-1203
DOI https://doi.org/10.1096/fj.201600749r
Keywords Cancer therapy, Hypertension, RTKI, VEGF, Regional hemodynamics
Public URL http://eprints.nottingham.ac.uk/id/eprint/39995
Publisher URL https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201600749R
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

Files


FASEB J-2016-Carter-fj.201600749R.pdf (1.9 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





You might also like



Downloadable Citations