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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/25394


    標題: KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways
    作者: Jwu-Lai Yeh
    Jong-Hau Hsu
    Ping-Ju Wu
    Shu-Fen Liou
    Chung-Pin Liu
    Ing-Jun Chen
    Bin-Nan Wu
    Zen-Kong Dai
    Jiunn-Ren Wu
    貢獻者: 藥學系
    關鍵字: KMUP-1
    cardiac hypertrophy
    isoprenaline
    nitric oxide
    calcineurin A
    日期: 2010-03
    上傳時間: 2012-06-05 10:10:33 (UTC+8)
    出版者: Wiley
    摘要: Background and purpose:  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.

    Experimental approach: 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, Nω-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.

    Key results: 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 and ERK1/2 in ISO-treated rats was also attenuated by KMUP-1. All these effects of KMUP-1 were inhibited by simultaneous administration of L-NNA. Similarly, in vitro, KMUP-1 attenuated hypertrophic responses and signalling induced by ISO in neonatal rat cardiomyocytes.

    Conclusions and implications:  KMUP-1 attenuates the cardiac hypertrophy in rats induced by administration of ISO. These effects are mediated, at least in part, by NOS activation. This novel agent, which targets the NO/cGMP pathway, has a potential role in the prevention of cardiac hypertrophy.
    關聯: British journal of pharmacology 159(5):p.1151-1160
    Appears in Collections:[藥學系(所)] 期刊論文

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