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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Effects of dimethylarginine dimethylaminohydrolase-1 overexpression on the response of the pulmonary vasculature to hypoxia
American Journal of Respiratory Cell and Molecular Biology, Volume 49, No. 3, Year 2013
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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 (DDAH1tg) 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, DDAH1tg 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 DDAH1tg. The administration of either Nω-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 DDAH1tg 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. Copyright © 2013 by the American Thoracic Society.
Authors & Co-Authors
Bakr, Adel G.
Egypt, Cairo
Faculty of Pharmacy
Pak, Oleg A.
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Taye, Ashraf Mohamed
Egypt, Minya
Faculty of Pharmacy
Hamada, Farid Mohamed Ahmed
Egypt, Cairo
Faculty of Pharmacy
Hemeida, Ramadan A.M.
Egypt, Cairo
Faculty of Pharmacy
Janssen, Wiebke
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Gierhardt, Mareike
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Ghofrani, Hossein Ardeschir
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Seeger, Werner
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Grimminger, Friedrich
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Schermuly, Ralph Theo
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Witzenrath, Martin
Germany, Berlin
Charité – Universitätsmedizin Berlin
Brandes, Ralf P.
Germany, Frankfurt am Main
Goethe-universität Frankfurt am Main
Huang, Ngan Fong Tina
United States, Stanford
Stanford University School of Medicine
Cooke, John P.
United States, Stanford
Stanford University School of Medicine
Weißmann, Norbert
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Sommer, Natascha
Germany, Giessen
Universities of Giessen and Marburg Lung Center
Statistics
Citations: 17
Authors: 17
Affiliations: 6
Identifiers
Doi:
10.1165/rcmb.2012-0330OC
ISSN:
10441549
e-ISSN:
15354989
Research Areas
Cancer
Noncommunicable Diseases