Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats
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 effe...
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Federation of American Society of Experimental Biology
2016
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| Online Access: | https://eprints.nottingham.ac.uk/39995/ |
| _version_ | 1848795961989529600 |
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| author | Carter, Joanne J. Fretwell, Laurice Woolard, Jeanette |
| author_facet | Carter, Joanne J. Fretwell, Laurice Woolard, Jeanette |
| author_sort | Carter, Joanne J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:40:25Z |
| format | Article |
| id | nottingham-39995 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T19:40:25Z |
| publishDate | 2016 |
| publisher | Federation of American Society of Experimental Biology |
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| spelling | nottingham-399952020-05-04T18:25:22Z https://eprints.nottingham.ac.uk/39995/ Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats Carter, Joanne J. Fretwell, Laurice Woolard, Jeanette 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. Federation of American Society of Experimental Biology 2016-12-16 Article PeerReviewed Carter, Joanne J., Fretwell, Laurice and Woolard, Jeanette (2016) Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. FASEB Journal . ISSN 1530-6860 Cancer therapy Hypertension RTKI VEGF Regional hemodynamics http://www.fasebj.org/content/early/2017/01/27/fj.201600749R doi:10.1096/fj.201600749R doi:10.1096/fj.201600749R |
| spellingShingle | Cancer therapy Hypertension RTKI VEGF Regional hemodynamics Carter, Joanne J. Fretwell, Laurice Woolard, Jeanette Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title | Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title_full | Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title_fullStr | Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title_full_unstemmed | Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title_short | Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| title_sort | effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats |
| topic | Cancer therapy Hypertension RTKI VEGF Regional hemodynamics |
| url | https://eprints.nottingham.ac.uk/39995/ https://eprints.nottingham.ac.uk/39995/ https://eprints.nottingham.ac.uk/39995/ |