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

Department of Cardiology, Yokohama Minami Kyosai Hospital, ashikaga-ind{at}umin.ac.jp

Mitsuhiro Nishizaki, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Hiroyuki Fujii, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Kensuke Ihara, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Saori Niki, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Tadashi Murai, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Shingo Maeda, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Noriyoshi Yamawake, MD

Department of Cardiology, Yokohama Minami Kyosai Hospital

Yukio Kishi, MD

Center for Preventive Medicine, Tokyo Kyosai Hospital

Mitsuaki Isobe, MD

Department of Cardiovascular Medicine, Tokyo Medical and the Dental University Japan

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.

Key Words: atrial natriuretic peptide • endothelial dysfunction • hyperinsulinemia

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