Dimethylarginine Dimethylaminohydrolase-1 Is the Critical Enzyme for Degrading the Cardiovascular Risk Factor Asymmetrical Dimethylarginine (original) (raw)

Objective— The objective of this study was to identify the role of dimethylarginine dimethylaminohydrolase-1 (DDAH1) in degrading the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and N g -monomethyl- l -arginine ( l -NMMA). Methods and Results— We generated a global-DDAH1 gene–deficient (DDAH1 −/− ) mouse strain to examine the role of DDAH1 in ADMA and l -NMMA degradation and the physiological consequences of loss of DDAH1. Plasma and tissue ADMA and l -NMMA levels in DDAH1 −/− mice were several folds higher than in wild-type mice, but growth and development of these DDAH1 −/− mice were similar to those of their wild-type littermates. Although the expression of DDAH2 was unaffected, DDAH activity was undetectable in all tissues tested. These findings indicate that DDAH1 is the critical enzyme for ADMA and l -NMMA degradation. Blood pressure was ≈20 mm Hg higher in the DDAH1 −/− mice than in wild-type mice, but no other cardiovascular phenotype was...