KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways.

British Journal of Pharmacology
Jwu-Lai YehJiunn-Ren Wu

Abstract

To determine whether KMUP-1, a novel xanthine-based derivative, attenuates isoprenaline (ISO)-induced cardiac hypertrophy in rats, and if so, whether the anti-hypertrophic effect is mediated by the nitric oxide (NO) pathway. In vivo, cardiac hypertrophy was induced by injection of ISO (5 mg.kg(-1).day(-1), s.c.) for 10 days in Wistar rats. In the treatment group, KMUP-1 was administered 1 h before ISO. After 10 days, effects of KMUP-1 on survival, cardiac hypertrophy and fibrosis, the NO/guanosine 3'5'-cyclic monophosphate (cGMP)/protein kinase G (PKG) and hypertrophy signalling pathways [calcineurin A and extracellular signal-regulated kinase (ERK)1/2] were examined. To investigate the role of nitric oxide synthase (NOS) in the effects of KMUP-1, a NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA) was co-administered with KMUP-1. In vitro, anti-hypertrophic effects of KMUP-1 were studied in ISO-induced hypertrophic neonatal rat cardiomyocytes. In vivo, KMUP-1 pretreatment attenuated the cardiac hypertrophy and fibrosis and improved the survival of ISO-treated rats. Plasma NOx (nitrite and nitrate) and cardiac endothelial NOS, cGMP and PKG were all increased by KMUP-1. The activation of hypertrophic signalling by calcineurin A a...Continue Reading

References

Jan 1, 1997·Annual Review of Physiology·J Sadoshima, S Izumo
Feb 22, 2001·Journal of Molecular and Cellular Cardiology·C MoriscoJ Sadoshima
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·I KishimotoD L Garbers
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Beate FiedlerKai C Wollert
Sep 13, 2002·Circulation Journal : Official Journal of the Japanese Circulation Society·Masanori OzakiMitsuhiro Yokoyama
Nov 2, 2002·Circulation Research·Orlando F Bueno, Jeffery D Molkentin
Feb 5, 2003·Cardiovascular Research·Anke C RosenkranzRebecca H Ritchie
Apr 7, 2004·Circulation·Norbert FreyJoseph A Hill
Sep 28, 2006·JAMA : the Journal of the American Medical Association·Keith D Aaronson, Jonathan Sackner-Bernstein
Jun 20, 2008·The International Journal of Biochemistry & Cell Biology·Joe W Ramos
Nov 1, 2008·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jiunn-Ren WuJwu-Lai Yeh

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Citations

Apr 16, 2011·International Journal of Biological Sciences·Xueying TanYanjie Lu
Jul 10, 2014·The American Journal of Chinese Medicine·Huai-Min ChenJwu-Lai Yeh
Aug 22, 2013·Physiology & Behavior·Cyrilla H WidemanHelen M Murphy
Sep 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chung-Pin LiuBin-Nan Wu
Dec 30, 2020·Journal of the American Heart Association·Xuejing SunJingjing Cai
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Wei-Lu WangYi-Zhun Zhu

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