Karen L. Andrews

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Until recently, most of the biological effects of nitric oxide (NO) have been attributed to its uncharged state (NO*), yet NO can also exist in the reduced state as nitroxyl (HNO or NO(-)). Putatively generated from both NO synthase (NOS)-dependent and -independent sources, HNO is rapidly emerging as a novel entity with distinct pharmacology and therapeutic(More)
BACKGROUND In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as(More)
BACKGROUND AND PURPOSE Nitroxyl (HNO) is emerging as an important regulator of vascular tone as it is potentially produced endogenously and dilates conduit and resistance arteries. This study investigates the contribution of endogenous HNO to endothelium-dependent relaxation and hyperpolarization in resistance arteries. EXPERIMENTAL APPROACH Rat and mouse(More)
Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO•), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and(More)
BACKGROUND Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO) bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II(More)
Vascular disease remains a major cause of morbidity and mortality in diabetes mellitus, in spite of recent improvements in outcome, some of which may be modulated by improved endothelial function. Therapeutic strategies aimed directly at preventing, or minimising the extent of, these sequelae are required as an adjunct to treatments directed at normalising(More)
1. The endothelium is critical in the control of vascular haemodynamics and haemostasis. Endothelial dysfunction, typically characterized by decreased nitric oxide bioavailability and response to endothelium-dependent agonists, is well accepted as a defining characteristic of early atherosclerosis. 2. Numerous epidemiological studies have reported that(More)
BACKGROUND AND PURPOSE Nitrate tolerance, the loss of vascular responsiveness with continued use of nitrates, remains incompletely understood and is a limitation of these therapeutic agents. Vascular superoxide, generated by uncoupled endothelial NOS (eNOS), may play a role. As arginase competes with eNOS for L-arginine and may exacerbate the production of(More)
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(More)
The ability of a series of novel imidazoline (IMID) compounds (fluoryl-, methoxy- and methyl-phenyl derivatives of clonidine) to inhibit the vasorelaxation and hyperpolarisation response to exogenous K+ (1–10 mM) was assessed in the rat middle cerebral artery (MCA) using the small vessel myograph. In this preparation, K+-induced relaxation was inhibited by(More)