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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tank, Jens Dietz, Rainer Bader, Michael Lindner, Maren Pagel-langenickel, Ines Buttgereit, Jens Beuerlein, Knut Al-saadi, Nidal Langenickel, Thomas H. Plehm, Ralph Willenbrock, Roland Popova, Elena Monti, Jan |
| Description | Author Affiliation: Langenickel TH ( Max Delbrück Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany. langenit@mail.nih.gov); |
| Abstract | Natriuretic peptides (NP) mediate their effects by activating membrane-bound guanylyl cyclase-coupled receptors A (NPR-A) or B (NPR-B). Whereas the pathophysiological role of NPR-A has been widely studied, only limited knowledge on the cardiovascular function of NPR-B is available. In vitro studies suggest antiproliferative and antihypertrophic actions of the NPR-B ligand C-type NP (CNP). Because of the lack of a specific pharmacological inhibitor, these effects could not clearly be attributed to impaired NPR-B signaling. Recently, gene deletion revealed a predominant role of NPR-B in endochondral ossification and development of female reproductive organs. However, morphological abnormalities and premature death of NPR-B-deficient mice preclude detailed cardiovascular phenotyping. In the present study, a dominant-negative mutant (NPR-BDeltaKC) was used to characterize CNP-dependent NPR-B signaling in vitro and in transgenic rats. Here we demonstrate that reduced CNP- but not atrial NP-dependent cGMP response attenuates antihypertrophic potency of CNP in vitro. In transgenic rats, NPR-BDeltaKC expression selectively reduced NPR-B but not NPR-A signaling. NPR-BDeltaKC transgenic rats display progressive, blood pressure-independent cardiac hypertrophy and elevated heart rate. The hypertrophic phenotype is further enhanced in chronic volume overload-induced congestive heart failure. Thus, this study provides evidence linking NPR-B signaling to the control of cardiac growth. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genes, Dominant Guanylate Cyclase Genetics Hypertrophy, Left Ventricular Physiopathology Receptors, Atrial Natriuretic Factor Animals Animals, Genetically Modified Blood Pressure Bone Development Cyclic GMP Metabolism Heart Rate Heart Ventricles Drug Effects Pathology Kidney Physiology Mutation Natriuretic Peptide, C-Type Pharmacology Sequence Deletion Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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