Acute Intravenous l -Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms

Abstract

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.

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

“…Exercise training may also be superior to peripheral angioplasty in improving exercise tolerance in such patients (27). Importantly, oral administration of L-arginine enhanced myocardial perfusion in coronary heart disease patients (44,(66)(67)(68)(69). In addition, L-arginine enhanced the beneficial effect of exercise on endothelial dysfunction in patients with heart failure (70).…”

Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice

“…However, it is conceivable that arterial cells can be affected by multiple signal transduction events promoted by early graduated PE. Short-term oral administration of L-arginine improved hemodynamics and PE capacity in patients with precapillary pulmonary hypertension (33) and enhanced myocardial perfusion in coronary heart disease patients (34)(35)(36)(37)(38)(39). In addition, oral Larginine supplementation enhanced the beneficial effect of PE training on endothelial dysfunction in patients with chronic heart failure (40).…”

Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting

“…20 Our group has previously suggested that a decrease of endothelin-1 levels, induced by L-arginine infusion, was able to restore insulin-induced NOx release in subjects with cardiovascular syndrome X. 21 A negative correlation between leptin levels and ⌬AUC-NOx (rϭϪ0.28; PϽ0.04; data not shown) was demonstrated and might support previous data by Cooke et al, 22 who postulated that the long-term consequence of hyperleptinemia is a reduction of NO synthesis attributable to the increased oxidative stress in endothelial cells. Still, the understanding of the molecular mechanisms that determine the impairment of NOx release in patients with restenosis is highly speculative and was beyond the scope of the present study.…”