Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Palmer, Richard; Ferrige, Anthony G.; Moncada, Salvador

doi:10.1038/327524a0

Cited by 9,990 publications

(4,602 citation statements)

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“…These in vivo observations would suggest that the mechanism reported here, namely lipoxin-induced prostacyclin generation by endothelium, can play a role in the intact circulatory system. In addition, lipoxins may also be involved in the release of other endothelialderived relaxing factors [20,21] such as nitric oxide [22]. On the other hand, the vasoconstriction of the splanchnic circulation observed upon systemic injection of lipoxin A4 and lipoxin B4 [7] may be mediated through their ability to generate other vasoactive agents such as thromboxane [16,17].…”

Section: Discussionmentioning

confidence: 99%

Lipoxins stimulate prostacyclin generation by human endothelial cells

et al. 1989

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Cultured human umbilical endothelial cells were incubated with lipoxins and their ability to generate prostacyclin (PGI,) was assessed and compared to that induced by either leukotriene C, or an ionophore of divalent cations (A-23,187). When exposed to either lipoxin 4, lipoxin B4, or 'I-cis.1 I-truns-lipoxin 4, endothelial cells generated prostacyclin detected as 6-keto-PGF,,. Of the lipoxins examined, 'I-c&l I-trans-lipoxin A., proved to be the most effective with PGI, production twice that induced by equimolar amounts of A-23,187 (5 PM). On a molar basis, lipoxin A., and lipoxin B4 were less potent than leukotriene C, although they were more efficacious. When either lipoxin A., or lipoxin B4 was added to cells simultaneously with leukotriene C,, the formation of prostacyclin was greater than that induced by leukotriene C, alone. During the time course of exposure to lipoxins (O-20 min, 37"C), cultured endothelial cells did not further transform these compounds via o-oxidation as determined by reverse-phase HPLC. These data indicate that lipoxins can stimulate PGI, generation by human endothelial cells. Moreover, they suggest a role for these lipoxygenase products of arachidonic acid in the regulation of hernostasis, inflammation and vascular reactivity.Arachidonic acid; Lipoxygenase product

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Section: Discussionmentioning

confidence: 99%

Lipoxins stimulate prostacyclin generation by human endothelial cells

et al. 1989

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“…This fact further amplifies the physiological and pathological significance of XOR. Unlike NO synthase, XOR can produce • NO under anoxic conditions and, thus, promote the • NO-dependent vasodilatation in ischaemic tissues [20]. On the other hand, ONOO -, a powerful oxidant and destructive agent, which results from the diffusioncontrolled reaction between • NO and O 2…”

Section: Introductionmentioning

confidence: 99%

NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production

et al. 2007

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To characterise the NADH oxidase activity of both xanthine dehydrogenase (XD) and xanthine oxidase (XO) forms of rat liver xanthine oxidoreductase (XOR) and to evaluate the potential role of this mammalian enzyme as an O 2•-source, kinetics and electron paramagnetic resonance (EPR) spectroscopic studies were performed. A steady-state kinetics study of XD showed that it catalyses NADH oxidation, leading to the formation of one O 2•-molecule and half a H 2 O 2 molecule per NADH molecule, at rates 3 times those observed for XO (29.2 ± 1.6 and 9.38 ± 0.31 min -1 , respectively). EPR spectra of NADHreduced XD and XO were qualitatively similar, but they were quantitatively quite different. While NADH efficiently reduced XD, only a great excess of NADH reduced XO. In agreement with reductive titration data, the XD specificity constant for NADH (8.73 ± 1.36 lM -1 min -1 ) was found to be higher than that of the XO specificity constant (1.07 ± 0.09 lM -1 min -1 ). It was confirmed that, for the reducing substrate xanthine, rat liver XD is also a better O 2•-source than XO. These data show that the dehydrogenase form of liver XOR is, thus, intrinsically more efficient at generating O 2•-than the oxidase form, independently of the reducing substrate. Most importantly, for comparative purposes, human liver XO activity towards NADH oxidation was also studied, and the kinetics parameters obtained were found to be very similar to those of the XO form of rat liver XOR, foreseeing potential applications of rat liver XOR as a model of the human liver enzyme.Keywords Xanthine oxidoreductase Á Xanthine oxidase Á Xanthine dehydrogenase Á Rat liver Á Reactive oxygen species Á NADH Abbreviations AFR Activity-to-flavin ratio AO Aldehyde oxidase EPR Electron paramagnetic resonance FAD Flavin adenine dinucleotide ROS Reactive oxygen species Sim Simulated XD Xanthine dehydrogenase XO Xanthine oxidase XOR Xanthine oxidoreductase

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“…What is the mechanism of ACh-mediated vasodilation? The vascular endothelium of large blood vessels synthesizes the vasodilator NO during exposure to acetylcholine [41,42]. Consistently, cholinergic vasodilation of murine retinal arterioles was also shown to be primarily mediated by NO, since blockade of NO production almost completely abolished responses to ACh.…”

Section: Neuronal Control Of Blood Flow: a Role For Cholinergic Regulmentioning

confidence: 79%

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

2016

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Optogenetic techniques are a powerful tool for determining the role of individual functional components within complex neural circuits. By genetically targeting specific cell types, neural mechanisms can be actively manipulated to gain a better understanding of their origin and function, both in health and disease. The potential of optogenetics is not limited to answering biological questions, as it is also a promising therapeutic approach for neurological diseases. An important prerequisite for this approach is to have an identified target with a uniquely defined role within a given neural circuit. Here, we examine the retinal neurovascular unit, a circuit that incorporates neurons and vascular cells to control blood flow in the retina. We highlight the role of a specific cell type, the cholinergic amacrine cell, in modulating vascular cells, and demonstrate how this can be targeted and controlled with optogenetics. A better understanding of these mechanisms will not only extend our understanding of neurovascular interactions in the brain, but ultimately may also provide new targets to treat vision loss in a variety of retinal diseases.

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Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Cited by 9,990 publications

References 0 publications

Lipoxins stimulate prostacyclin generation by human endothelial cells

Lipoxins stimulate prostacyclin generation by human endothelial cells

NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production

Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

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