Inhalation of an endothelin receptor A antagonist attenuates pulmonary inflammation in experimental acute lung injuryThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin
| Autor: | Christian Bauer, Bodil Petersen, Berthold Hocher, Willehad Boemke, Philine SenfP. Senf, Philipp Kalk, Thilo Busch, Maria Deja, U. Kaisers |
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| Rok vydání: | 2008 |
| Předmět: |
Pharmacology
medicine.medical_specialty Inhalation Physiology business.industry medicine.medical_treatment Antagonist Histology General Medicine Oxygenation Lung injury respiratory tract diseases Surgery Physiology (medical) medicine.artery Pulmonary artery medicine Endothelin receptor business Saline |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 86:511-515 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y08-046 |
| Popis: | We recently demonstrated that inhalation of the endothelin receptor A (ETA) antagonist LU 135252 improved arterial oxygenation and reduced pulmonary artery pressure in experimental acute lung injury (ALI). In this study we analyzed potential immune modulatory effects of inhaled LU 135252 in experimental ALI. ALI was induced by repeated lung lavage in intubated (100% O2) and anesthetized piglets. Animals were randomly assigned to inhale either nebulized LU 135252 (0.3 mg·kg–1, ALI + LU group, n = 8) or saline buffer (ALI control group, n = 16), both for 30 min. Surviving animals were sacrificed 6 h after induction of ALI, and lung tissue specimens were obtained from all animals for histology and immunhistochemistry. Induction of ALI significantly decreased arterial oxygenation in all animals. Inhalation of LU 135252 significantly reduced mortality and induced significant and sustained increase in Pao2 (316 ± 47 mm Hg vs. control 53 ± 3 mm Hg, p < 0.001). We measured a significant reduction in the number of pulmonary leukocyte L1 antigen-positive cells in ALI + LU animals (8% ± 1% positive cells vs. control 12% ± 2% positive cells, p < 0.05). The number of CD3-positive cells was not altered by treatment with LU 135252. Pulmonary tissue concentration of IL-6 was significantly suppressed by LU 135252 inhalation (4 ± 1 pg·100 mg–1 wet weight vs. control 7 ± 1 pg·100 mg–1 wet weight, p < 0.05). Concentrations of TNF-α, IL-1β, and ET-1 in pulmonary tissue were not influenced by inhalation of LU 135252. In conclusion, we demonstrated that inhalation of LU 135252 not only improves mortality and gas exchange, but also blunts the local immune response in experimental ALI. |
| Databáze: | OpenAIRE |
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