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.
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.


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.
Piatti
PierMarco
P
Divisione di Medicina, Unità di Diabetologia, Endocrinologia e Malattie Metaboliche, Dipartimento di Cardiologia e Scienze Cardiovascolari, Unità di Cardiologia Clinica, IRCCS H San Raffaele, Milano, Italy. piermarco.piatti@hsr.it
Fragasso
Gabriele
G
Monti
Lucilla D
LD
Setola
Emanuela
E
Lucotti
Pietro
P
Fermo
Isabella
I
Paroni
Rita
R
Galluccio
Elena
E
Pozza
Guido
G
Chierchia
Sergio
S
Margonato
Alberto
A
D000787:Angina Pectoris / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D017023:Coronary Angiography; D006152:Cyclic GMP / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D013577:Syndrome
D019332:Endothelin-1; D007328:Insulin; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D006152:Cyclic GMP