The anti-inflammatory agents Siblings Nitroxyl (HNO) and Nitric Oxide (NO) in Cardioprotection

Author(s): Claudia Penna, Donatella Gattullo, Pasquale Pagliaro

Journal Name: Drug Design Reviews - Online (Discontinued)

Volume 1 , Issue 4 , 2004


Abstract:

Nitric oxide (NO) and nitrogen oxide species have been shown to be critical elements in most physiological functions in the cardiovascular system. The chemical unbalance of these species results in progression of disease. Until recent, most of the focus of nitrogen oxide chemistry has been on the effect NO and oxidized progenitors have on cardiovascular system. Recently, nitroxyl (HNO / NO-) the one electron reduced species of NO has been shown to have unique and possible pharmaceutically beneficial properties. These properties are often the opposite of those of NO and provide an interesting paradigm. This review will discuss novel and emerging aspects of HNO and NO unique effects in vivo and in vitro. Cardioprotective mechanisms such as acute or early preconditioning triggered by NO and nitroxyl will be analyzed. Preconditioning includes several primary signaling pathways that seem to converge on mitochondrial targets, leading to altered cell metabolism and inhibition of apoptosis. Brief ischemia leads to generation of agonists that bind to G protein-coupled receptors, and initiates a signaling cascade that involves activation of phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, mitogen-activated protein kinases, and other signaling pathways. Activation of these pathways along with generation of reactive oxygen species leads to alterations in the activity of mitochondrial proteins such as mitochondrial ATP-sensitive K+ channels, thus resulting in cardioprotection.

Keywords: anti-inflammatory agents, protein kinase C, ischemia, cardioprotection

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Article Details

VOLUME: 1
ISSUE: 4
Year: 2004
Page: [273 - 285]
Pages: 13
DOI: 10.2174/1567269043390609
Price: $58

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