on January 13, 2003
Published online before print January 13, 2003, doi: 10.1161/01.CIR.0000046489.24563.79
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Submitted on July 30, 2002
From Divisione di Medicina, Unitá di Diabetologia, Endocrinologia e Malattie Metaboliche (P.P., L.D.M., E.S., P.L., E.G.), Cattedra di Clinica Medica Generale e Terapia Medica (G.P.), Università Vita-Salute (G.F., S.C., A.M.), Laboratorio di Tecniche Separative (I.F., R.P.), Dipartimento di Cardiologia e Scienze Cardiovascolari, Unità di Cardiologia Clinica, IRCCS H San Raffaele, Milano, Italy. * To whom correspondence should be addressed. E-mail: piermarco.piatti{at}hsr.it.
Background--We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects. Methods and Results--Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after L-arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, L-arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, L-arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, L-arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release. Conclusions--Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous L-arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.
Revised on October 8, 2002
Accepted on October 8, 2002
Acute Intravenous L-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms. Correlation With Asymmetric Dimethylarginine Levels
PierMarco Piatti MD*,
Key words: endothelin • nitric oxide • amino acids • angina • arteries
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