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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents

ID: 711845.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
Structural and functional prevention of hypoxia-induced pulmonary hypertension by individualized exercise training in mice
Authors:Weissmann, N.; Peters, D. M.; Klopping, C.; Kruger, K.; Pilat, C.; Katta, S.; Seimetz, M.; Ghofrani, H. A.; Schermuly, R. T.; Witzenrath, M.; Seeger, W.; Grimminger, F.; Mooren, F. C.
Date of Publication (YYYY-MM-DD):2014-06-01
Title of Journal:Am J Physiol Lung Cell Mol Physiol
Issue / Number:11
Start Page:L986
End Page:95
Audience:Not Specified
Abstract / Description:Pulmonary hypertension (PH) is a disease with a poor prognosis characterized by a vascular remodeling process and an increase in pulmonary vascular resistance. While a variety of reports demonstrated that exercise training exerts beneficial effects on exercise performance and quality of life in PH patients, it is not known how physical exercise affects vascular remodeling processes occurring in hypoxia-induced PH. Therefore, we investigated the effect of individualized exercise training on the development of hypoxia-induced PH in mice. Training effects were compared with pharmacological treatment with the phosphodiesterase 5 inhibitor Sildenafil or a combination of training plus Sildenafil. Trained mice who received Sildenafil showed a significantly improved walking distance (from 88.9 +/- 8.1 to 146.4 +/- 13.1 m) and maximum oxygen consumption (from 93.3 +/- 2.9 to 105.5 +/- 2.2% in combination with Sildenafil, to 102.2 +/- 3.0% with placebo) compared with sedentary controls. Right ventricular systolic pressure, measured by telemetry, was at the level of healthy normoxic animals, whereas right heart hypertrophy did not benefit from training. Most interestingly, the increase in small pulmonary vessel muscularization was prevented by training. Respective counterregulatory processes were detected for the nitric oxide-soluble guanylate cyclase-phosphodiesterase system. We conclude that individualized daily exercise can prevent vascular remodeling in hypoxia-induced PH.
Free Keywords:3',5'-Cyclic-AMP Phosphodiesterases/genetics/metabolism; Animals; Anoxia/complications/*therapy; Exercise Therapy; Exercise Tolerance; Gene Expression; Hypertension, Pulmonary/etiology/*prevention & control; Lung/blood supply/metabolism; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular/physiopathology; Nitric Oxide Synthase/genetics/metabolism; Oxygen Consumption; Phosphodiesterase 5 Inhibitors/pharmacology; Physical Conditioning, Animal; Piperazines/pharmacology; Purines/pharmacology; Signal Transduction; Sulfones/pharmacology; Ventricular Pressure; Sildenafil; chronic hypoxia; maximal walking distance; pulmonary vascular remodeling; training
External Publication Status:published
Document Type:Article
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany; Department of Sports Medicine, Justus Liebig-University Giessen, Giessen, Germany; Division of Infectiology and Pneumology, Charite-Universitatsmedizin Berlin Medical Clinic, Berlin, Germany; and. Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany; Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany. %^ 1435822045
Identifiers:ISSN:1522-1504 (Electronic) 1040-0605 (Linking) %R 10.1152/ajplung.00275.2013
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