Acute microvascular effects of PAF-acether, as studied by intravital microscopy

Björk, Jakob; Smedegård, G.

doi:10.1016/0014-2999(83)90532-0

Cited by 111 publications

(41 citation statements)

References 20 publications

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“…Mediator-stimulated increase in protein extravasation is primarily attributable to an increase in the hydraulic conductivity of the microvascular membrane (Grega et al, 1986). All inflammatory mediators evaluated to date, including autacoids, anaphylatoxins and free radicals, induce interendothelial cell gap formation exclusively in the venules (Bjork & Smedegard, 1983;Grega et al, 1986). This leads to opening of the variable large-pore system, the dominant macromolecular transport pathway operant in inflammation (Grega et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Filep¹,

Sirois

Rousseau

et al. 1991

British J Pharmacology

106

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The objectives of the present experiments were to assess the effects of endothelin‐1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet‐activating factor (PAF) in vascular responses to endothelin‐1 and to examine the vascular effects of combined administration of endothelin‐1 and PAF in conscious rats. Intravenous bolus injection of endothelin‐1 (0.1–2 nmol kg−1) resulted in a dose‐dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose‐dependent increase in haematocrit values. Endothelin‐1 (0.1 and 1 nmol kg−1) increased dose‐dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin‐1 treatment. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg−1, i.v.) or BN 52021 (10 mg kg−1, i.v.) reduced the endothelin‐1 (1 nmol kg−1)‐induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin‐1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin‐1. When low doses of endothelin‐1 (0.1 nmol kg−1) and PAF (0.19 nmol kg−1) were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin‐1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP. Combined administration of higher doses of endothelin‐1 (1 nmol kg−1) and PAF (1.9 nmol kg−1) resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin‐1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin‐1 and PAF resulted in a slight, but significant increase in MABP. The present findings show that endothelin‐1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin‐1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

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Section: Discussionmentioning

confidence: 99%

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Filep¹,

Sirois

Rousseau

et al. 1991

British J Pharmacology

106

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“…These two mechanisms were initially ' Author for correspondence. described in rabbit skin (Wedmore & Williams, 1981a) but were later found to occur in hamsters (Bjork & Smedegard), 1983), rats (Mulligan et al, 1992b), mice (Perretti et al, 1993) and also in man (Williamson et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea‐pig skin: contribution of neutrophils and endogenous mediators

Teixeira

Fairbairn

Norman

et al. 1994

British J Pharmacology

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1 Mediators of inflammation can increase vascular permeability in at least two different ways: by acting directly on endothelial cells or, indirectly, through an incompletely understood mechanism, dependent on circulating neutrophils. Neutrophil-dependent oedema formation has been described in the skin of rabbits, rats, hamsters, mice and man. In contrast, we presented evidence in a previous study that local oedema formation induced by i.d. injection of chemoattractants in guinea-pig skin was neutrophil-independent. In the present study, we sought evidence of neutrophil-dependent oedema formation in immune-complex-mediated vasculitis, the reversed passive Arthus (RPA) reaction, in guinea-pig skin. We also investigated whether haemorrhage in the RPA reaction was neutrophildependent (as it is in other species) and the role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in contributing to the local inflammatory response. 2 In the RPA reaction, most oedema formation occurred over the first 60 min whereas "'In-neutrophil accumulation was still increasing from 60 to 240 min. The different kinetics of these two events suggested that they may be dissociated.3 Oedema formation was partially inhibited by a long-acting PAF antagonist (UK-74,505) and an HI histamine receptor antagonist (mepyramine) but not by a 5-lipoxygenase inhibitor (ZM 230487). A nitric oxide synthesis inhibitor (NW-nitro-L-arginine methyl ester, L-NAME) suppressed oedema formation by 68% whereas a cyclo-oxygenase inhibitor suppressed oedema by 27%. 4 "'In-neutrophil accumulation in the RPA reaction was partially suppressed by UK-74,505. In contrast, ZM 230487 was without effect at doses which abrogated arachidonic acid-induced "'Inneutrophil accumulation. 5The anti-CD18 monoclonal antibody, (mAb) 6.5E F(ab')2, effectively inhibited "'In-neutrophil accumulation induced by PAF, zymosan-activated plasma (ZAP) and in the RPA reaction. However, oedema formation measured in the same sites was not altered. In contrast, oedema formation in the RPA reaction was partially suppressed by 6.5E whole mAb which was 2.5 times more potent than 6.5E F(ab')2 at inhibiting guinea-pig neutrophil adhesion to protein-coated plastic. Haemorrhage induced by PAF and in the RPA reaction was significantly inhibited by 6.5E F(ab')2 pretreatment. 6 We conclude that in the RPA reaction in guinea-pig skin, oedema formation is partially neutrophildependent as assessed by using an anti-CD18 mAb, whereas ZAP-induced oedema formation is neutrophil-independent. Haemorrhage was also dependent on neutrophil accumulation. In addition, our studies support a role for PAF in mediating both oedema formation and "'In-neutrophil accumulation in the RPA reaction. Endogenous release of histamine also appears to be important in mediating oedema formation suggesting that mast cells play a critical role in increases of vascular permeability in inflammatory reactions in guinea-pig skin. Moreover, our results confirm previous findings which suggest...

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“…Inflammatory mediators released in COPD may contribute to bronchial vasodilation [5] and potential candidates include bradykinin [6], prostaglandins [7] and neuropeptides released by sensory nerves [8]. Platelet-activating factor (PAF) may also increase bronchial vascular blood flow [9]. Bronchial blood flow may be reduced because of the low bronchial vascularity [2], the vasoconstrictive effect of endothelins [10] and hyperinflation, which decreases bronchial blood flow.…”

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confidence: 99%

Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease

Paredi¹,

Caramori²,

Cramer³

et al. 2003

Eur Respir J

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In chronic obstructive pulmonary disease (COPD) there is decreased vascularity of the bronchi and inflammation of the airways that may have opposite effects on the regulation of heat loss.Exhaled air temperature increase (DeuT) was measured in 23 patients with moderate COPD (18 male, mean age¡SEM 70¡1 yrs; forced expiratory volume in one second (FEV1) 45¡3%, FEV1/forced vital capacity 54¡4%) and 16 normal volunteers (64¡4 yr) and compared to exhaled nitric oxide (eNO) and inflammatory cells in induced sputum as a marker of airway inflammation. DeuT was measured during a flowand pressure-controlled single exhalation with a fast-response thermometer.DeuT was reduced in patients with COPD (1.86¡0.15 DuC?s -1 ) compared to normal subjects (4.00¡0.26 DuC?s -1 ). There was no difference in DeuT between patients treated with inhaled steroids and those who were steroid naïve. DeuT was correlated with eNO (r=0.60) but not with sputum neutrophilia. In COPD patients, DeuT was increased (2.26¡0.16 DuC?s -1 ) after the inhalation of 200 mg of albuterol, which is a known vasodilator, indicating that DeuT and bronchial blood flow may be correlated.Exhaled temperature increase is reduced in chronic obstructive pulmonary disease patients and is increased by the inhalation of vasodilators and therefore may be related to changes of bronchial blood flow and tissue remodelling.

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Acute microvascular effects of PAF-acether, as studied by intravital microscopy

Cited by 111 publications

References 20 publications

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea‐pig skin: contribution of neutrophils and endogenous mediators

Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease

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