Coronary Endothelial Dysfunction and Impaired Microcirculation Response to Atrial Natriuretic Peptide in Hyperinsulinemia

Abstract

Endothelial dysfunction occurs in hyperinsulinemia (HI). Coronary microcirculation responses to vasoactive agents are examined in 57 patients with angiographically normal coronary arteries. Patients were divided into 2 groups, 37 with normoinsulinemia (NI) and 20 with HI based on results of a 75-g oral glucose tolerance test. Epicardial artery vasoactivity in response to acetylcholine chloride is measured to assess endothelial function. Coronary microcirculation function is evaluated by intracoronary administration of 50 µg of adenosine triphosphate, 1 mg of isosorbide dinitrate, and 0.05 mg/kg of atrial natriuretic peptide. Epicardial artery vasoconstriction in response to 100 µg of acetylcholine is mildly reduced in HI ( P = .04). Coronary flow reserve in response to adenosine triphosphate in NI is similar to that in HI. In NI, the resting mean (SD) peak velocity in response to isosorbide dinitrate (40.7 [10.9] cm/s) vs atrial natriuretic peptide (39.6 [10.9] cm/s) is similar. In contrast, the resting mean (SD) peak velocity in response to atrial natriuretic peptide (31.3 [9.3] cm/s) vs isosorbide dinitrate (43.5 [10.0] cm/s) in HI is statistically significantly blunted ( P < .001). Atrial natriuretic peptide may have a pathologic effect on coronary microcirculation even in mild endothelial dysfunction among patients with HI.