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. 1995 Jul;115(5):753–760. doi: 10.1111/j.1476-5381.1995.tb14997.x

A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats.

C Herbst 1, B Tippler 1, H Shams 1, T Simmet 1
PMCID: PMC1908526  PMID: 8548173

Abstract

1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P < 0.01) and arterial CO2 partial pressure (PaCO2) significantly increased from 4.64 +/- 0.56 kPa to 8.15 +/- 0.99 kPa (P < 0.01). Gradually a progressive acidosis developed. Moreover, mean arterial blood pressure (MABP) and end-inspiratory airway pressure (Paw) rapidly increased. 3. Concomitantly there was a time-dependent increase of big ET-1 and ET-1 levels in bronchoalveolar lavage (BAL) as determined by combined reverse phase high performance liquid chromatography (h.p.l.c.) and radioimmunoassay. BAL levels of both peptides increased up to 8 min after bicuculline injection and slowly decreased subsequently. In contrast, BAL from animals injected with vehicle did not contain detectable amounts of ET. 4. Pretreatment with the endothelin-converting enzyme inhibitor, phosphoramidon (5.4 mg kg-1, i.v.) for 5 min significantly (P < 0.001) reduced peak ET-1 levels in BAL fluid by 65.4 +/- 9.9% at 8 min after bicuculline injection. Simultaneously it afforded protection from hypoxia. PaCO2 did not increase and PaO2 decreased only slightly from 14.63 +/- 1.00 kPa to 12.97 +/- 0.61 kPa (P > 0.05) after phosphoramidon pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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