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Nitroxyl (HNO) as a Vasoprotective Signaling Molecule
被引:62
作者:
Bullen, Michelle L.
[1
]
Miller, Alyson A.
[1
]
Andrews, Karen L.
[2
]
Irvine, Jennifer C.
[3
]
Ritchie, Rebecca H.
[3
]
Sobey, Christopher G.
[1
]
Kemp-Harper, Barbara K.
[1
]
机构:
[1] Monash Univ, Dept Pharmacol, Vasc Biol & Immunopharmacol Grp, Clayton, Vic 3800, Australia
[2] Baker IDI Heart & Diabet Inst, Dept Vasc Pharmacol, Melbourne, Vic, Australia
[3] Baker IDI Heart & Diabet Inst, Dept Heart Failure Pharmacol, Melbourne, Vic, Australia
基金:
英国医学研究理事会;
澳大利亚国家健康与医学研究理事会;
关键词:
NO-CENTER-DOT;
SOLUBLE GUANYLATE-CYCLASE;
HYDROXY-L-ARGININE;
NITRIC-OXIDE NO;
GENE-RELATED PEPTIDE;
SMOOTH-MUSCLE;
SUPEROXIDE-PRODUCTION;
VASCULAR DYSFUNCTION;
BIOLOGICAL-ACTIVITY;
POTENT VASODILATOR;
D O I:
10.1089/ars.2010.3327
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO center dot), is rapidly emerging as a novel nitrogen oxide with distinct pharmacology and therapeutic advantages over its redox sibling. Whilst the cardioprotective effects of HNO in heart failure have been established, it is apparent that HNO may also confer a number of vasoprotective properties. Like NO center dot, HNO induces vasodilatation, inhibits platelet aggregation, and limits vascular smooth muscle cell proliferation. In addition, HNO can be putatively generated within the vasculature, and recent evidence suggests it also serves as an endothelium-derived relaxing factor (EDRF). Significantly, HNO targets signaling pathways distinct from NO center dot with an ability to activate K-V and K-ATP channels in resistance arteries, cause coronary vasodilatation in part via release of calcitonin-gene related peptide (CGRP), and exhibits resistance to scavenging by superoxide and vascular tolerance development. As such, HNO synthesis and bioavailability may be preserved and/or enhanced during disease states, in particular those associated with oxidative stress. Moreover, it may compensate, in part, for a loss of NO center dot signaling. Here we explore the vasoprotective actions of HNO and discuss the therapeutic potential of HNO donors in the treatment of vascular dysfunction. Antioxid. Redox Signal. 14, 1675-1686.
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页码:1675 / 1686
页数:12
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