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Analysis of ET-A and ET-B receptors using an isolated perfused rat lung preparation

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AIMS AND METHODS: The pulmonary and vascular effects of endothelin-1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin-1 (ET-1) and the endothelin B (ET(B)) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET(A))-receptor antagonist FR 139317, the ET(B)-receptor antagonist BQ 788 and the combined ET(A)/ET(B)-receptor antagonist Bosentan. The respiratory parameter airway conductance (G(aw)) and the vascular parameter perfusion flow were analysed simultaneously.

RESULTS: Concentration-response curves for ET-1 administered intra-arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET-1, given as a bolus dose intra-arterially (100 microL of 0.2 nM), induced a strong- and long-lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G(aw) or perfusion flow. FR 139317 reduced the effect of ET-1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET-1 while G(aw) was not influenced. The combined ET(A)/ET(B) antagonist Bosentan powerfully prevented the ET-1-induced decrease in G(aw) but did not alter its reduction in perfusion flow.

CONCLUSIONS: The potent effect of ET-1 on the vascular side of the lung is mediated mainly through ET(A) receptors, whereas both ET(A) and ET(B) receptors are involved in G(aw) in the rat lung.

Original languageEnglish
JournalActa Physiologica Scandinavica. Supplementum
Volume181
Issue number2
Pages (from-to)259-64
Number of pages6
ISSN0001-6772
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

    Research areas

  • Animals, Antihypertensive Agents, Azepines, Bronchi, Endothelin A Receptor Antagonists, Endothelin B Receptor Antagonists, Endothelin-1, Indoles, Lung, Male, Oligopeptides, Organ Culture Techniques, Perfusion, Piperidines, Rats, Rats, Sprague-Dawley, Receptor, Endothelin A, Receptor, Endothelin B, Sulfonamides, Vasoconstrictor Agents, Viper Venoms

ID: 44900447