An <i>in vivo</i> model for measuring antigen‐induced SRS‐A‐mediated bronchoconstriction and plasma S RS‐ A levels in the guinea‐pig

Anderson, Wayne H.; O’Donnell, Margaret; Simko, B.; Welton, Ann F.

doi:10.1111/j.1476-5381.1983.tb09363.x

Cited by 93 publications

(41 citation statements)

References 39 publications

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“…Thus in both cases the predominant mediators responsible for the residual bronchospasm in the presence of anti-histamine and cyclo-oxygenase blockade appear to be leukotrienes, as has been previously found with i.v. challenge (Ritchie et al, 1981;Anderson et al, 1983). It is possible that following a low challenge stimulus (microshock), a redirection of arachidonic acid metabolism (with increased leukotriene production) may occur, whereas following a high challenge stimulus (macroshock) and lipoxygenase pathway is already maximally stimulated.…”

Section: Ovalbumin Macroshockmentioning

confidence: 99%

“…challenge in the alation of presence of a histamine H,-receptor antagonist (Rit-1987). This chie et al, 1981;Anderson et al, 1983). In the latter uantitative situation, indomethacin had been used to enhance in airway histamine-independent resistant bronchospasm.…”

Section: Ovalbumin Macroshockmentioning

confidence: 99%

“…We believe that this method of challenge is preferable to the intravenous route, since the antigen is delivered directly to the airway smooth muscle rather than via the vasculature. Furthermore, both the physiological and pathological sequelae of aerosol challenge in guinea-pigs are known to closely resemble human asthma (Kallos & Kallos, 1984 (Darius et al, 1986;Pretolani et al, valbumin, 1986 (Ritchie et al, 1981;Anderson et al, 1983).…”

Section: Ovalbumin Macroshockmentioning

confidence: 99%

“…This compound has previously been demonstrated to inhibit 'leukotriene dependent' anaphylactic bronchospasm in guinea-pigs following either i.v. (Ritchie et al, 1981;Anderson et al, 1983) or (in passively sensitized animals) aerosol challenge (Saga et al, 1984). In the present study we evaluated the effect of BW755C under the same pretreatment conditions (combination of a histamine H,-receptor antagonist and indomethacin).…”

Section: Ovalbumin Macroshockmentioning

confidence: 99%

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Pharmacological modulation of bronchial anaphylaxis induced by aerosol challenge in anaesthetized guinea‐pigs

Daffonchio

Lees

Payne

et al. 1987

British J Pharmacology

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Anaphylactic bronchoconstriction provoked by aerosol challenge, and its pharmacological modulation, has been investigated in anaesthetized pump‐ventilated guinea‐pigs actively sensitized to ovalbumin (OA). Aerosol challenge (OA 0.03–10 mg ml−1) provoked immediate bronchoconstriction, the degree of which, and its rate of development, was directly related to antigen concentration. Concomitant changes in heart rate and systemic arterial blood pressure following aerosol challenge were reduced compared with systemic (OA, 1 mg kg−1 i.v.) challenge. Unlike systemic challenge, aerosol challenge did not cause a concomitant fall in either circulating leukocyte or platelet count. When a submaximal (microshock) aerosol challenge stimulus (OA, 0.3 mg ml−1, 5 s) was employed, bronchoconstriction was markedly reduced by mepyramine (2 mg kg−1 i.v.). The residual component of bronchoconstriction was enhanced by indomethacin (10 mg kg−1 i.v.), an effect which was reversed by either BW755C (30 mg kg−1 i.v.) or FPL55712 (10 mg kg−1 i.v.). When a supramaximal (macroshock) aerosol challenge stimulus (OA, 10 mg ml−1, 5 s) was employed, bronchoconstriction was also markedly reduced by mepyramine. Residual bronchoconstriction was not altered by indomethacin, slowed but not reduced by indomethacin plus BW755C, and substantially reduced by indomethacin plus FPL55712. The successive incremental antagonism of anaphylactic bronchoconstriction by mepyramine and mepyramine plus indomethacin and FPL55712 indicates that the predominant mediators involved are histamine and leukotrienes, respectively. The failure of indomethacin plus BW755C to inhibit the mepyramine‐resistant bronchoconstriction provoked by OA macroshock may reflect the increased generation of leukotrienes via a 5‐lipoxygenase isoenzyme resistant to inhibition by BW755C. Aerosol challenge of actively sensitized anaesthetized guinea‐pigs by this method may be a useful model of human allergic bronchoconstriction, particularly when the effects of a drug given itself as an aerosol are being evaluated.

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Section: Ovalbumin Macroshockmentioning

confidence: 99%

Section: Ovalbumin Macroshockmentioning

confidence: 99%

Section: Ovalbumin Macroshockmentioning

confidence: 99%

Section: Ovalbumin Macroshockmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological modulation of bronchial anaphylaxis induced by aerosol challenge in anaesthetized guinea‐pigs

Daffonchio

Lees

Payne

et al. 1987

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Th plasma supernatant was then decanted into a test tube, extracted with 4 volumes of absolute ethanol, and allowed to stand on ice for 30 min. The precipitated protein was removed by centrifugation at 25,000 x g for 30 min at 4°C (Anderson et al 1983). The ethanol supernatant was evaporated under vacuum at 35°C.…”

Section: Methodsmentioning

confidence: 99%