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

ID: 474445.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
The soluble guanylate cyclase activator HMR1766 reverses hypoxia-induced experimental pulmonary hypertension in mice
Authors:Weissmann, N.; Hackemack, S.; Dahal, B. K.; Pullamsetti, S. S.; Savai, R.; Mittal, M.; Fuchs, B.; Medebach, T.; Dumitrascu, R.; Eickels, M.; Ghofrani, H. A.; Seeger, W.; Grimminger, F.; Schermuly, R. T.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Am J Physiol Lung Cell Mol Physiol
Issue / Number:4
Start Page:L658
End Page:65
Audience:Not Specified
Abstract / Description:Severe pulmonary hypertension (PH) is a disabling disease with high mortality, characterized by pulmonary vascular remodeling and right heart hypertrophy. In mice with PH induced by chronic hypoxia, we examined the acute and chronic effects of the soluble guanylate cyclase (sGC) activator HMR1766 on hemodynamics and pulmonary vascular remodeling. In isolated perfused mouse lungs from control animals, HMR1766 dose-dependently inhibited the pressor response of acute hypoxia. This dose-response curve was shifted leftward when the effects of HMR1766 were investigated in isolated lungs from chronic hypoxic animals for 21 days at 10% oxygen. Mice exposed for 21 or 35 days to chronic hypoxia developed PH, right heart hypertrophy, and pulmonary vascular remodeling. Treatment with HMR1766 (10 mg x kg(-1) x day(-1)), after full establishment of PH from day 21 to day 35, significantly reduced PH, as measured continuously by telemetry. In addition, right ventricular (RV) hypertrophy and structural remodeling of the lung vasculature were reduced. Pharmacological activation of oxidized sGC partially reverses hemodynamic and structural changes in chronic hypoxia-induced experimental PH.
Free Keywords:Animals; Anoxia/*prevention & control; Anthranilic Acids/*pharmacology; Cardiomegaly; Cyclic GMP/metabolism; Guanylate Cyclase/*metabolism; Hemodynamics/drug effects; Hypertension, Pulmonary/enzymology/*prevention & control; Mice; Myocytes, Smooth Muscle/drug effects/metabolism; Pulmonary Artery/cytology/drug effects/metabolism; Receptors, Cytoplasmic and Nuclear/*metabolism; Sulfonamides/*pharmacology; Superoxides/metabolism; Vasoconstriction/drug effects
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Univ. of Giessen Lung Center Medical Clinic II/V, Klinikstr. 36, 35392 Giessen, Germany.
Identifiers:ISSN:1522-1504 (Electronic) 1040-0605 (Linking)
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