Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan

Schroll, Stephan and Arzt, Michael and Sebah, Daniela and Nuechterlein, Martin and Blumberg, Friedrich and Pfeifer, Michael (2010) Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan. RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 170 (1). pp. 32-36. ISSN 1569-9048,

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Abstract

Rationale: There is evidence that endothelin plays a key role in the development of pulmonary hypertension (PH) in pulmonary fibrosis (PF). However, the functional consequence of the unselective endothelin receptor antagonist Bosentan in PH and PF has not yet been studied. Therefore, we investigated the effects of Bosentan on the development of PH in the model of Bleomycin-induced PF in rats. Methods: Adult male Wistar rats were randomly assigned to the following groups: untreated animals (controls), Bleomycin-induced PF (Bleomycin) and Bleomycin-induced PF treated with Bosentan (Bleomycin+Bosentan). Exercise capacity was evaluated by treadmill exercise testing. PH was assessed by right ventricular systolic pressure (RVSP) and right ventricular hypertrophy. For quantification of PF the hydroxyproline content in lung tissue (HPC) was measured. Results: Compared to controls, animals with Bleomycin-induced PFshowed a significant reduction in exercise capacity (44% vs. 100%), significantly higher RVSP (65 mmHg vs. 23 mmHg), significantly more right ventricular hypertrophy (0.55 vs. 0.24) and significantly higher HPC (60.5 vs. 14.8). Bosentan treatment in animals with Bleomycin-induced PF resulted in significantly greater exercise capacity (98% vs. 44%) and a trend towards lower RVSP (52 mmHg vs. 65 mmHg), significantly less right ventricular hypertrophy (0.34 vs. 0.55) and significantly lower HPC (16.7 vs. 60.5) compared to untreated Bleomycin-induced PF. Conclusion: Application of Bosentan in Bleomycin rats resulted in significantly higher exercise capacity as a result of improvements in PH and PF. (C) 2009 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: TISSUE GROWTH-FACTOR; ARTERIAL-HYPERTENSION; INTRATRACHEAL BLEOMYCIN; BRONCHOALVEOLAR LAVAGE; SURVIVAL; EXPRESSION; RAT; FIBROBLASTS; PATHOGENESIS; INFLAMMATION; Pulmonary hypertension; Pulmonary fibrosis; Endothelin; Bleomycin; Bosentan; Exercise capacity
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 10 Aug 2020 07:49
Last Modified: 10 Aug 2020 07:49
URI: https://pred.uni-regensburg.de/id/eprint/25285

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