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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\u2013450 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 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05;\n                    <jats:italic>n<\/jats:italic>\n                    = 7\u20138) 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.\u2014Carter, J. J., Fretwell, L. V., Woolard, J. Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. FASEB J. 31,1193\u20131203 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600749r","type":"journal-article","created":{"date-parts":[[2016,12,16]],"date-time":"2016-12-16T21:15:16Z","timestamp":1481922916000},"page":"1193-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats"],"prefix":"10.1096","volume":"31","author":[{"given":"Joanne J.","family":"Carter","sequence":"first","affiliation":[{"name":"Cell Signalling Research Group School of Life Sciences Medical School The University of Nottingham Queen's Medical Centre  Nottingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurice V.","family":"Fretwell","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences De Montfort University  Leicester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette","family":"Woolard","sequence":"additional","affiliation":[{"name":"Cell Signalling Research Group School of Life Sciences Medical School The University of Nottingham Queen's Medical Centre  Nottingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,12,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.13.130"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1684\/ecn.2009.0170","article-title":"VEGF-A: a critical regulator of blood vessel growth","volume":"20","author":"Ferrara N.","year":"2009","journal-title":"Eur. 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