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Plasma Concentration of Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Is Elevated in Hyperthyroid Patients

Departamentos de Fisiología (C.H., P.M., M.P., G.S., J.M.V., S.L.) and Cirugía (J.O.), Universidad de Valencia and Research Unit (C.H.), Hospital Clínico Universitario de Valencia, E-46010 Valencia, Spain

Address all correspondence and requests for reprints to: Dr. Pascual Medina, Departamento de Fisiología, Facultad de Medicina y Odontología, Blasco Ibáñez 17, 46010 Valencia, Spain. E-mail: medinap{at}post.uv.es.

Abstract

Cardiovascular manifestations are frequent findings in patients with thyroid hormone disorders. Nitric oxide (NO) plays a key role in vascular, endothelial-mediated relaxation. NO is synthesized from L-arginine by NO synthase, an enzyme inhibited by endogenous compounds, mainly asymmetric dimethylarginine [asymmetric N^G,N^G-dimethyl-L-arginine (ADMA)]. The aim of our work was to investigate whether plasma L-arginine and dimethylarginine concentrations and NO production are altered in hypo- and hyperthyroid patients, compared with control subjects. L-arginine, ADMA and symmetric dimethylarginine were analyzed by HPLC. NO was measured as plasma nitrite plus nitrate (NO_x) concentration by a colorimetric method based on Griess reagent. L-arginine, ADMA, and symmetric dimethylarginine plasma levels in the hypothyroid group were similar to those of the control group; whereas in hyperthyroidism, these values were significantly increased. However, the L-arginine/ADMA ratio was decreased in hyperthyroid patients, resulting in diminished NO_x production. When all subjects were analyzed together, free T₄ levels were directly correlated with ADMA and inversely correlated with NO_x.

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