Nitroxyl (HNO) as a vasoprotective signaling molecule.
Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO(•)), 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(•), 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(•) 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(•) signaling. Here we explore the vasoprotective actions of HNO and discuss the therapeutic potential of HNO donors in the treatment of vascular dysfunction.
Bullen
Michelle L
ML
Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Miller
Alyson A
AA
Andrews
Karen L
KL
Irvine
Jennifer C
JC
Ritchie
Rebecca H
RH
Sobey
Christopher G
CG
Kemp-Harper
Barbara K
BK
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009589:Nitrogen Oxides / Q000378:metabolism*; D015398:Signal Transduction; D014664:Vasodilation
D045462:Endothelium-Dependent Relaxing Factors; D009589:Nitrogen Oxides; C039900:nitroxyl; D015740:Calcitonin Gene-Related Peptide