Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682239.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Effects of dimethylarginine dimethylaminohydrolase-1 overexpression on the response of the pulmonary vasculature to hypoxia
Authors:Bakr, A.; Pak, O.; Taye, A.; Hamada, F.; Hemeida, R.; Janssen, W.; Gierhardt, M.; Ghofrani, H. A.; Seeger, W.; Grimminger, F.; Schermuly, R. T.; Witzenrath, M.; Brandes, R. P.; Huang, N.; Cooke, J. P.; Weissmann, N.; Sommer, N.
Date of Publication (YYYY-MM-DD):2013-09
Journal Abbrev.:Am J Respir Cell Mol Biol
Volume:49
Issue / Number:3
Start Page:491
End Page:500
Audience:Not Specified
Abstract / Description:Acute and sustained hypoxic pulmonary vasoconstriction (HPV), as well as chronic pulmonary hypertension (PH), is modulated by nitric oxide (NO). NO synthesis can be decreased by asymmetric dimethylarginine (ADMA), which is degraded by dimethylarginine dimethylaminohydrolase-1 (DDAH1). We investigated the effects of DDAH1 overexpression (DDAH1(tg)) on HPV and chronic hypoxia-induced PH. HPV was measured during acute (10 min) and sustained (3 h) hypoxia in isolated mouse lungs. Chronic PH was induced by the exposure of mice to 4 weeks of hypoxia. ADMA and cyclic 3',5'-guanosine monophosphate (cGMP) were determined by ELISA, and NO generation was determined by chemiluminescence. DDAH1 overexpression exerted no effects on acute HPV. However, DDAH1(tg) mice showed decreased sustained HPV compared with wild-type (WT) mice. Concomitantly, ADMA was decreased, and concentrations of NO and cGMP were significantly increased in DDAH1(tg). The administration of either Nomega-nitro-l-arginine or 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one potentiated sustained HPV and partly abolished the differences in sustained HPV between WT and DDAH1(tg) mice. The overexpression of DDAH1 exerted no effect on the development of chronic hypoxia-induced PH. DDAH1 overexpression selectively decreased the sustained phase of HPV, partly via activation of the NO-cGMP pathway. Thus, increased ADMA concentrations modulate sustained HPV, but not acute HPV or chronic hypoxia-induced PH.
Free Keywords:Amidohydrolases/*genetics/metabolism; Animals; Anoxia/complications/*genetics/metabolism/physiopathology; Arginine/analogs & derivatives/*metabolism; Blood Vessels/drug effects/physiopathology; Cyclic GMP/metabolism; Gene Expression; Hemodynamics/drug effects; Hypertension, Pulmonary/etiology/*genetics/metabolism/physiopathology; Lung/drug effects/*metabolism/physiopathology; Mice; Nitric Oxide/*metabolism; Nitroarginine/pharmacology; Organ Culture Techniques; Oxadiazoles/pharmacology; Signal Transduction; Vasoconstriction/drug effects
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1535-4989 (Electronic) 1044-1549 (Linking) %R 10.1165/rcmb.2012-0330OC
URL:http://www.ncbi.nlm.nih.gov/pubmed/23642043
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.