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Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia

Arrigoni, FI; Vallance, P; Haworth, SG; Leiper, JM; (2003) Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation , 107 (8) 1195 - 1201. 10.1161/01.CIR.0000051466.00227.13. Green open access

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Abstract

BACKGROUND: Nitric oxide (NO) plays an important part in lowering pulmonary vascular resistance after birth, and in persistent pulmonary hypertension of the newborn (PPHN), NO-mediated dilation is dysfunctional. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) circulates in plasma, and its concentrations are elevated in certain cardiovascular diseases, including pulmonary hypertension. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the activity of which regulates ADMA concentrations and provides a mechanism for modulating NO synthase in vivo. We investigated the changes in expression and activity of the 2 isoforms of DDAH in lungs from newborn piglets both during normal development and in PPHN. METHODS AND RESULTS: Using Western blotting, we showed that DDAHI expression did not change in the normal developing lung; however, DDAHII increased after birth and reached a peak at 1 day. This was reflected in an increase in total DDAH activity according to an L-citrulline assay. With pulmonary hypertension, no changes in DDAHI expression were observed, but DDAHII expression was markedly decreased compared with age-matched controls. Total DDAH activity was similarly reduced. CONCLUSIONS: These results indicate that each DDAH isoform is differentially regulated during both lung development and PPHN. Suppression of DDAHII isoform expression may be a mechanism underlying PPHN

Type:Article
Title:Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia
Open access status:An open access version is available from UCL Discovery
DOI:10.1161/01.CIR.0000051466.00227.13
Keywords:activity, Amidohydrolases, analogs & derivatives, analysis, Animals, Newborn, Anoxia, Arginine, ASSAY, biosynthesis, BIRTH, cardiovascular, cardiovascular disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, complications, Concentration, control, developing, development, disease, Diseases, embryology, endogenous, enzyme, enzymology, etiology, expression, genetics, growth & development, Hypertension, Pulmonary, hypoxia, IM, Immunohistochemistry, in vivo, in-vivo, INCREASE, INDICATE, INHIBITOR, isoform, ISOFORMS, LA, Lung, LUNG DEVELOPMENT, Male, May, MECHANISM, metabolism, Methods, NEWBORN, nitric oxide, NITRIC-OXIDE, NO CHANGE, OXIDE, PERSISTENT, plasma, play, Pressure, PROTEIN, Protein Isoforms, pulmonary, PULMONARY HYPERTENSION, rats, Rats, Sprague-Dawley, Resistance, Result, Rna, RNA, Messenger, Support, Non-U.S.Gov't, SUPPRESSION, Swine, SYNTHASE, vascular, Vascular Resistance, vivo, western blotting, Hypertension
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health

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