Role of inducible nitric oxide synthase in endothelium‐independent relaxation to raloxifene in rat aorta

Wong, Chi Ming; Au, Chak Leung; Tsang, Suk Ying; Lau, Chi Wai; Yao, Xiaoqiang; Cai, Zongwei; Chung, Arthur C.K.

doi:10.1111/bph.13733

Cited by 12 publications

(10 citation statements)

References 51 publications

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“…In this study, nitric oxide (NO) and tumor necrosis factor (TNF)‐α were used as indicators to assess the anti‐inflammatory activity of ASR . Treatment by ASR significantly reduced NO and TNF‐α release in lipopolysaccharide (LPS)‐ and adenosine triphosphate (ATP)‐stimulated BV2 microglia.…”

Section: Introductionmentioning

confidence: 99%

“…13,14,17 In this study, nitric oxide (NO) and tumor necrosis factor (TNF)-α were used as indicators to assess the anti-inflammatory activity of ASR. 18,19 Treatment by ASR significantly reduced NO and TNF-α release in lipopolysaccharide (LPS)-and adenosine triphosphate (ATP)-stimulated BV2 microglia. Using benzylamine as a substrate, in vitro enzyme inhibition assay results showed that the IC 50 of ASR to MAO-B was 1.611 mg/mL, suggesting that this TCM formula contains compounds with MAO-B inhibitory activity.…”

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confidence: 99%

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Chemical characterization of small‐molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry

Wang

Zhang

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Discovering and identifying new small‐molecule inhibitors of monoamine oxidase B (MAO‐B) could provide the potential to treat many neurodegenerative diseases. Methods We employed affinity ultrafiltration liquid chromatography/tandem mass spectrometry (AUF‐LC/MSn) to identify and characterize small‐molecule inhibitors of MAO‐B from a 30% ethanolic extract of Acanthopanax senticosus root (ASR). In vitro tests were performed in stimulated BV2 microglia to evaluate the anti‐inflammatory effects of the ASR preparation. An in vitro enzyme activity assay, measuring half‐maximal inhibitory concentrations (IC50) against MAO‐B, determined the inhibitory activity of the potential MAO‐B ligands. Results ASR treatment significantly inhibited NO release (p <0.01) and attenuated tumor necrosis factor (TNF)‐α expression in stimulated BV2 microglia. Nine compounds were isolated from the ASR preparation as potential MAO‐B inhibitors, identified as quinic acid, chlorogenic acid, isofraxidin, dicaffeoylquinic acid, pinoresinol diglucoside, medioresinol 4’‐O‐β‐D‐glucopyranoside, eletutheroside E, syringaresinol O‐β‐D‐glucoside, and trihydroxyoctadecenoic acid, based on their tandem mass spectra. Conclusions Our study provides critical data on compounds from ASR extracts which are suitable for the development of new MAO‐B inhibitors as potential therapeutics for neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Chemical characterization of small‐molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry

Wang

Zhang

et al. 2020

Rapid Comm Mass Spectrometry

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“…NO is an intracellular messenger discovered in recent years, which may play a role in information transmission in the central nervous system (Wong et al, 2017). NO can be produced by L-arginine catalyzed by nitric oxide synthase (NOS) (Grasemann et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Ketamine Anesthesia on Neurocyte in Fetal Rat via cAMP and NO/cGMP Pathway

Chen¹

2019

PVJ

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Ketamine anesthesia during infancy has an impact on development of nervous system. This study is to demonstrate effects of ketamine on neuronal cells via cAMP and NO-cGMP pathway. The cortex neurocyte of Wistar fetal rat were divided into four groups. Every group was given different doses, low dose group was 0.7 μg/mL, anesthesia groups were 1 μg/mL, 3 μg/mL, 5 μg/mL at 0, 5, 10, 15, 20, 25, 30, 45, 60, 90 and 120 min, respectively. The content of cGMP and cAMP were detected by ELISA, and the activity of NOS and content of NO were detected by spectrophotometric method. After different concentrations of ketamine were applied to isolated neurons, cAMP and cGMP levels were lowered first and then increased, the content reached the bottom at 25 min and then increased. In the 30 min, the content of NO and NOS decreased to the lowest value and then went up, respectively. In the 120 min, their values were both lower than 0 min. Ketamine probably expressed its anesthesia effect with the increasement of cAMP and inhibition of NO-cGMP pathway. L, 2019. Ketamine anesthesia on neurocyte in fetal rat via camp and NO/cGMP pathway. Pak Vet J, 39(2): 246-250. http://dx.

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“…In their recent article, Wong et al . () report a number of observations and conclusions that are difficult to reconcile, both methodologically and mechanistically. The authors state that in endothelium‐denuded aortic rings of male Sprague–Dawley rats, raloxifene at concentrations of 1 μM caused ‘a time‐dependent relaxant response for 3 h’ that was mediated by inducible NOS (iNOS or NOS2).…”

Section: Nomenclature Of Targets and Ligandsmentioning

confidence: 99%

Rapid vasodilation to raloxifene: role of oestrogen receptors and off‐target effects

Barton

Prossnitz

2017

British J Pharmacology

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For decades, raloxifene has been recognized as mediating the rapid, non-genomic relaxation of endothelium-intact and endothelium-denuded arteries of many species. In their recent article, Wong et al. (2017) report a number of observations and conclusions that are difficult to reconcile, both methodologically and mechanistically. The authors state that in endothelium-denuded aortic rings of male Sprague-Dawley rats, raloxifene at concentrations of 1 μM caused 'a time-dependent relaxant response for 3 h' that was mediated by inducible NOS (iNOS or NOS2).According to information provided in the 'Materials' section, the authors did not individually determine optimal length-tension curves (by repeated exposure to high K + ) but simply added a passive tension of 1 g. This is substantially below the normally employed tension for rat aorta (typically between 2 and 4 g), and no repeated passive-tension curves to KCl were performed for each individual ring to determine its optimal passive tension. Moreover, due to the lack of an internal contractility standard for each ring, the degree of precontraction induced by each drug relative to KCl cannot be ascertained, and it is therefore possible that given the concentrations of U46619 used, the contractions exceeded those evoked by 60 mM KCl, which would have the effect of directly affecting (i.e. reducing) relaxant responses as the artery was initially 'overcontracted'. This may, in part, even explain the delayed relaxant response to raloxifene, which in previous studies has been shown to occur within minutes and, as with oestradiol or ICI 182,780 (Meyer et al., 2010), is usually reached within 40 min. Furthermore, the authors' claim that the relaxation response requires a full 3 h is not supported by the data: As seen in Figure 4B, C, the onset of relaxation is observed by 20 min and the pD 2 is reached after about 40 min (and 50-60 min in Figures 2, 3 and 5). The time courses of the 'original tracings' also reveal that the authors did not wait until a stable contraction plateau was reached but added drugs or solvent upon reaching the maximum contraction, without allowing the vessel to equilibrate. Thus, the reported responses could have represented either a simple decrease of tone during the plateauing phase or a spontaneous loss of tone prior to reaching the plateau, which is frequently observed in this preparation. Also, the original tracings of the raloxifene response are in fact identical in three figures (2A, 3A and 4A), and the onset of relaxation in these 'representative' tracings is not mirrored by the analysed cumulative data presented. Furthermore, as there was little additional relaxation to raloxifene observed beyond 80-90 min, waiting a further 90 min to measure NOS2 expression makes little sense. Increased NOS2 expression at 3 h post-stimulation does not explain relaxant responses observed as early as 20 min following raloxifene treatment, a time when changes in NOS2 protein expression would not be expected. It is also possible that additional factors, such as...

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Role of inducible nitric oxide synthase in endothelium‐independent relaxation to raloxifene in rat aorta

Cited by 12 publications

References 51 publications

Chemical characterization of small‐molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry

Chemical characterization of small‐molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry

Ketamine Anesthesia on Neurocyte in Fetal Rat via cAMP and NO/cGMP Pathway

Rapid vasodilation to raloxifene: role of oestrogen receptors and off‐target effects

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