• Giovanni Li Volti, Valeria Sorrenti, Rosaria Acquaviva, Paolo Murabito, Antonino Gullo, Maria Luisa Barcellona, Fabio Galvano, Luigi Rodella, Rita Rezzani, Luca Vanella, Giovanni Tringali, Massimo Caruso, Diego Gazzolo, and Claudia Di Giacomo.
• Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Italy. livolti@unict.it
• Anesthesiology. 2008 Dec 1; 109 (6): 105410621054-62.

BackgroundAsymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. It is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH).MethodsRats (n = 50) underwent to 45 min of renal ischemia followed by 30 min, 1 h, and 3 h of reperfusion. Expression of endothelial nitric oxide synthase, inducible nitric oxide synthase, DDAH-1, DDAH-2, renal DDAH activity, plasma NO2(-)/NO3(-), and ADMA levels were evaluated.ResultsInducible nitric oxide synthase expression increased, as confirmed by both plasma (11.89 +/- 1.02, 15.56 +/- 0.93, 11.82 +/- 0.86, 35.05 +/- 1.28, and 43.89 +/- 1.63 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (4.81 +/- 0.4, 4.85 +/- 1, 9.42 +/- 0.7, 15.42 +/- 0.85, and 22.03 +/- 1.11 nmol/mg protein) formations of NO2(-)/NO3(-). DDAH-1 expression decreased after reperfusion, whereas DDAH-2 increased after 30 min, returning to basal levels after 3 h. Total DDAH activity was reduced during all times of reperfusion. Both plasma (0.41 +/- 0.03, 0.43 +/- 0.05, 0.62 +/- 0.02, 0.71 +/- 0.02, and 0.41 +/- 0.01 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (1.51 +/- 0.01, 1.5 +/- 0.01, 1.53 +/- 0.01, 2.52 +/- 0.04, and 4.48 +/- 0.03 nmol/mg protein in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) concentrations of ADMA increased.ConclusionsResults suggest that ischemia-reperfusion injury leads to reduced DDAH activity and modification of different DDAH isoform expression, thus leading to increased ADMA levels, which may lead to increased cardiovascular risk.

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