OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ('cardiac' syndrome X [CSX]) compared with subjects with insulin resistance syndrome ('metabolic' syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (ΔAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 ± 0.46 and 6.97 ± 0.88 vs. 3.67 ± 0.99 pg/ml; p <0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 ± 4.0 vs. 24.2 ± 3.3 and 26.8 ± 3.2 mol/liter, p <0.05). After insulin administration, the ΔAUCs of NOx (p <0.05) were lower in CSX group than in MSX and normal controls, and the ΔAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p <0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the ΔAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.
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