Reversal effects of low-dose imatinib compared with sunitinib on monocrotaline-induced pulmonary and right ventricular remodeling in rats

Vascular Pharmacology
Zi Ping LeongYoshiaki Hikasa

Abstract

High-dose imatinib reverses cardiopulmonary remodeling but adverse effects limit its clinical use. Efficacy of the multi-kinase inhibitor sunitinib remains questionable. We compared anti-remodeling effects of imatinib with sunitinib on monocrotaline-induced right ventricular (RV) hypertrophy and pulmonary arterial remodeling in rats, focusing on a lower dose. Fourteen days after monocrotaline injection, oral gavage of imatinib (5, 15, or 50mg/kg), sunitinib (0.3, 1, 3, or 10mg/kg), or water for 14days was started. RV hypertrophy and b-type natriuretic peptide mRNA levels were significantly and dose-dependently reduced, much greater in imatinib- than sunitinib-treated groups. Imatinib normalized muscularization of 20-50μm intra-acinar pulmonary arteries more significantly than sunitinib. At transcript levels, sunitinib significantly upregulated pulmonary nestin, and downregulated platelet-derived growth factor receptor beta (PDGFR-β), fibroblast growth factor receptor 1, vascular endothelial growth factor receptor-2 and vascular endothelial growth factor (VEGF)-A, but not Raf-1 proto-oncogene serine/threonine kinase mRNAs. Sunitinib also suppressed VEGF-A, but not phosphorylated extra-cellular-signal-related kinase (ERK)-1/2 pro...Continue Reading

Citations

Nov 12, 2019·British Journal of Pharmacology·Astrid WeissRalph T Schermuly
Mar 7, 2021·Pediatric Research·Catheline HocqUNKNOWN from the European Society for Pediatric Research

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