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Disruption of methylarginine metabolism impairs vascular homeostasis
It is shown that loss of DDAH-1 activity leads to accumulation of ADMA and reduction in NO signaling, which causes vascular pathophysiology, including endothelial dysfunction, increased systemic vascular resistance and elevated systemic and pulmonary blood pressure, and it is suggested that DDAh inhibition could be harnessed therapeutically to reduce the vascular collapse associated with sepsis. Expand
Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase.
In vivo administration of substrate-based inhibitors of mammalian DDAH increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAh inhibition, with potential for pharmaceutical use of D DAH inhibitors in diseases where excess NO production is implicated. Expand
11 beta-hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver.
The substantial concentrations of plasma 11-DHC as substrate suggest that 11 beta-HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo. Expand
Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis.
An efficient process for the discovery of inhibitors of DDAH enzymes, without the requirement for high throughput screening, is described. Physicochemical filtering of a 308,000-compound libraryExpand
Inhibition of dimethylarginine dimethylaminohydrolase (DDAH) and arginine deiminase (ADI) by pentafluorophenyl (PFP) sulfonates.
A range of pentafluorophenyl (PFP) sulfonate esters derived from the reaction of PFP vinyl sulfonate and various nitrones are shown to have significant inhibitory activity against the bacterialExpand
Halogenated indole-3-acetic acids as oxidatively activated prodrugs with potential for targeted cancer therapy.
Halogenated IAAs were found to be the most cytotoxic, with typical surviving fractions of <10(-3) after incubation for 2h with 100 microM prodrug and HRP. Expand
Nω-Nitro-L-Arginine Methyl Ester Reduces the Incidence of IDDM in BB/E Rats
Evidence that nitric oxide (NO) is involved in cytokine-mediated islet β-cell dysfunction and destruction in vitro has led to the hypothesis that increased production of NO may contribute to theExpand
In vivo and in vitro evidence of altered nitric oxide metabolism in the spontaneously diabetic, insulin‐dependent BB/Edinburgh rat
Although diabetic BB/E rats do not achieve overall normoglycaemia, individual adjustment of the daily insulin dose administered to every diabetic rat achieves better glycaemic control than previous groups studying altered vascular reactivity and endothelial dysfunction in this animal model of diabetes. Expand