Imatinib Attenuates End-Organ Damage in Hypertensive Homozygous TGR(mRen2)27 Rats

Imatinib specifically inhibits receptor tyrosine kinase signaling and is clinically used to treat leukemia. Receptor tyrosine kinases not only mediate tumor growth but also initiate adverse signaling in heart failure. We investigated whether imatinib, by inhibiting the platelet-derived growth factor...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2006-03, Vol.47 (3), p.467-474
Main Authors: Schellings, Mark W.M, Baumann, Marcus, van Leeuwen, Rick E.W, Duisters, Rudy F.J.J, Janssen, Suzanne H.P, Schroen, Blanche, Peutz-Kootstra, Carine J, Heymans, Stephane, Pinto, Yigal M
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Arterioles - drug effects
Arterioles - pathology
Benzamides
Blood Pressure - drug effects
Cells, Cultured
Fibrosis
Heart Diseases - prevention & control
Hemodynamics - drug effects
Homozygote
Hypertension - complications
Hypertension - genetics
Imatinib Mesylate
Kidney - blood supply
Kidney Diseases - prevention & control
Kidney Glomerulus - drug effects
Kidney Glomerulus - pathology
Kidney Tubules - drug effects
Kidney Tubules - pathology
Male
Myocardium - pathology
Piperazines - pharmacology
Protein Kinase Inhibitors - pharmacology
Pyrimidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases - genetics
Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors
Receptor, Platelet-Derived Growth Factor beta - metabolism
Renin - genetics
Signal Transduction - drug effects
Transcriptional Activation - drug effects
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Summary:Imatinib specifically inhibits receptor tyrosine kinase signaling and is clinically used to treat leukemia. Receptor tyrosine kinases not only mediate tumor growth but also initiate adverse signaling in heart failure. We investigated whether imatinib, by inhibiting the platelet-derived growth factor receptor-β (PDGFRβ), prevents cardiac and renal damage in TGR(mRen2)27 (Ren2) rats. Eight-week-old male homozygous Ren2 and Sprague Dawley rats were treated either with imatinib (30 mg/kg; STI-571) or placebo for 8 weeks (Ren2 n=12 for each group; Sprague Dawley n=6 for each group). Imatinib did not affect blood pressure or left ventricular (LV) hypertrophy in both groups. Imatinib attenuated the decline in fractional shortening (imatinib versus Ren2 placebo 45±4.5% versus 32±3%; n=7–11; P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000202487.68969.f7