Regulation of lung endothelin content by the glucocorticosteroid budesonide

Andersson, Sven; Zackrisson, C.; Hemsén, Anette; Lundberg, Jan M.

doi:10.1016/0006-291x(92)91347-s

Cited by 29 publications

(25 citation statements)

References 16 publications

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“…Firstly, respiratory tract viral infection in mice is associated with the generation and release of numerous mediators and cytokines (Hennet et al, 1992) some of which stimulate the enhanced synthesis and release of endothelin-1 from airway epithelial cells (Endo et al, 1992). Secondly, enhanced synthesis and release of endothelin-1 from the airway wall has been demonstrated in inflammatory diseases of the airways, such as asthma and in animal models of airway inflammation (Springall et al, 1991;Vittori et al, 1992;Andersson et al, 1992). Like asthma, respiratory tract viral infection is associated with epithelial cell damage and airway wall inflammation which may trigger enhanced release of endothelin-1.…”

Section: Discussionmentioning

confidence: 99%

ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

Henry

Goldie

1994

British J Pharmacology

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1 The current study investigated the effects of respiratory tract viral infection on the density of ETA and ETB receptors in murine tracheal smooth muscle and on the contractile response to endothelin-1 mediated by these receptors. 2 Quantitative autoradiographic studies using ['251]-endothelin-l revealed that tracheal smooth muscle from control mice contained ETA and ETB receptors in the ratio of 42%:58% ( + 4%, n = 10 mice), respectively. In contrast, tracheal smooth muscle obtained from mice 2 days post-inoculation with Influenza A/PR-8/34 virus contained 23 ± 2% fewer receptors for ['25I]-endothelin-l (n = 10, P<0.01).This reflected a selective reduction in ETB receptor density and a change in the ratio of ETA and ETB receptors to 77% :23% ( ± 5%, n = 10 mice), respectively. 3 The ETB receptor-selective agonist, sarafotoxin S6c, was a potent spasmogen of murine isolated tracheal smooth muscle and the EC50 for contraction was similar in preparations from control (3.6 nM [95% confidence limits, 2.7-4.8 nM], n = 16 preparations from 8 mice) and virus-inoculated mice (3.0 nM [2.4-3.7 nM], n = 16 preparations from 8 mice). However, the maximum contractions induced by sarafotoxin S6c (100 nM) in the preparations from virus-inoculated mice (37 ± 5% Cm., where 100%Cm., was the response to 10IM carbachol) were significantly smaller than those from control mice (85±4% Cmax, P<0.01). 4 Contractions induced by endothelin-1 in tracheal smooth muscle preparations obtained from virusinoculated mice (EC" for contraction, 6.5 nM [95% confidence limits, 2.7-16 nM]; maximum contraction, 112 ± 5% Cm.; n = 4) were similar to those induced by endothelin-1 in control preparations (ECm 9.3 nM (4.2-21); maximum contraction, 110 ± 3% C,,,.a; n = 4). Endothelin-1-induced contractions in control preparations were only marginally inhibited by the ETA receptor-selective antagonist BQ-123 (in the presence of 3 jLM BQ-123; EC50 for contraction, 5.9 nM [4.1-8.5]; maximum contraction, 82 ± 4% Cx,,,; n = 4). In contrast, 3 tiM BQ-123 caused a 50 fold rightward shift (17-160, n =4) of the concentration-effect curve to endothlin-1 in preparations obtained from virus-inoculated mice (measured at the 30% C=,, level of contraction). 5 Tracheal smooth muscle preparations exposed to 100 nM sarafotoxin S6c for 30 min (followed by a 30 min washout period) did not contract to subsequently administered sarafotoxin S6c (1-100 nM; n = 8), but contracted normally in response to endothelin-1 (EC50 6.5 nM (2.3-18); maximum contraction, 109 ± 2% Cm,,; n = 4). Endothelin-l-induced contractions in these ETB receptor desensitized preparations were markedly inhibited by 3 ILM BQ-123, irrespective of whether the preparations were obtained from control (63 fold shift (10-400) at the 30% Cma. level of contraction, n = 4) or virusinoculated mice (46 fold shift (18-120), n = 4). 6 In summary, tracheal smooth muscle obtained from mice infected with a respiratory tract virus, Influenza A/PR-8/34 had a reduced density of ETB receptors and an attenuated ETB receptor-med...

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Section: Discussionmentioning

confidence: 99%

ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

Henry

Goldie

1994

British J Pharmacology

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“…Intratracheal (IT) LPS instillation in rats induces a massive infiltration of neutrophils in lung tissue, a pattern with similarities to human adult respiratory distress syndrome (ARDS) [10]. This neutrophilic inflammation was compared to the eosinophilic inflammation induced by intratracheally instillation of the dextran Sephadex (SDX), which promotes a strong production of ET-1 [1,2,11].…”

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Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

et al. 2000

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Endothelin‐1 (ET‐1) is a strong bronchoconstrictor which possesses pro‐inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET‐1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET‐1 and tumour necrosis factor (TNF)‐α in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET‐1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six‐fold increase was measured after 30 min in the SDX group (p<0.05). TNF‐α mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF‐α mRNA in the SDX model was observed at 24 h. The ET‐1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET‐1 levels was observed in the LPS model, while a substantial increase in the ET‐1 concentration was measured in the SDX group (p<0.05). The TNF‐α concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF‐TNF‐α did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin‐1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin‐1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin‐1 synthesis was observed by high levels of tumour necrosis factor‐αin vivo.

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“…In a previous work [11], we have shown that the amount of ET-l-like immunoreactivity (ET-l-LI) is markedly elevated in lung homogenates from rats in which an inflammatory reaction in the lungs was induced by the intratracheal (i.t.) instillation of dextran (Sephadex beads).…”

Section: Introductionmentioning

confidence: 99%

“…The response to Sephadex instillation is otherwise characterized by an influx of inflammatory cells, mainly eosinophils, and a long-lasting interstitial oedema [11. 12], At low doses the glucocorticosteroid budesonide inhibits both the oedema formation and the rise in ETl-LI content in lung parenchyma [11,13],…”

Section: Introductionmentioning

confidence: 99%

Release of Endothelin-1 into Rat Airways following Sephadex-Induced Inflammation; Modulation by Enzyme Inhibitors and Budesonide

Andersson

Hemsén²,

Zackrisson³

et al. 1996

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The intratracheal (i.t.) instillation of Sephadex beads into the rat induced inflammation and a 30-fold increase in the endothelin-1-like immunoreactivity (ET-1-LI) of broncho-alveolar lavage fluid. The levels were highest 24 h after the instillation and had declined significantly after 48 h. At a dose of 1 mg kg^-1 i.t., the glucocorticosteroid budesonide almost abolished this response. Phosphoramidon, which inhibits neutral endopeptidase, an enzyme reported to degrade ET-1 and also to inhibit the endothelin-converting enzyme, potentiated the Sephadex-induced rise in ET-1-LI. Chymostatin and heparin, which are reported to reduce the formation of ET-1, did not affect the increase in ET-l-LI. The present model represents a very reactive system for analyzing the changes in ET-1 levels during inflammation.

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Regulation of lung endothelin content by the glucocorticosteroid budesonide

Cited by 29 publications

References 16 publications

ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Release of Endothelin-1 into Rat Airways following Sephadex-Induced Inflammation; Modulation by Enzyme Inhibitors and Budesonide

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Regulation of lung endothelin content by the glucocorticosteroid budesonide

Cited by 29 publications

References 16 publications

ETB but not ETA receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

ETB but not ETA receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Release of Endothelin-1 into Rat Airways following Sephadex-Induced Inflammation; Modulation by Enzyme Inhibitors and Budesonide

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ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

ET_B but not ET_A receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways