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(Circulation. 2005;111:288-294.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Role of ß₂ Adrenergic Receptors in Human Atherosclerotic Coronary Arteries

Emanuele Barbato, MD; Federico Piscione, MD, PhD; Jozef Bartunek, MD, PhD; Gennaro Galasso, MD; Plinio Cirillo, MD, PhD; Giuseppe De Luca, MD; Guido Iaccarino, MD, PhD; Bernard De Bruyne, MD, PhD; Massimo Chiariello, MD, PhD; William Wijns, MD, PhD

From the Divisions of Cardiology (E.B., F.P., G.G., P.C., G.D.L., M.C.) and Internal Medicine (G.I.), Federico II University of Naples, Italy; and the Cardiovascular Center OLVZ, Aalst, Belgium (E.B., J.B., B.D.B., W.W.).

Correspondence to Federico Piscione, MD, Division of Cardiology, Federico II University, Via Pansini, 5, 80131 Naples, Italy. E-mail piscione{at}unina.it or emanuele.barbato@uniroma1.it

Received June 19, 2004; revision received October 8, 2004; accepted October 21, 2004.

Background— Adrenergic regulation of coronary vasomotion is balanced between ₁-adrenergic–mediated (₁-AR) constriction and ß₂-adrenergic–mediated (ß₂-AR) relaxation. This study aimed at assessing the role of ß₂-ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries.

Methods and Results— During intracoronary (IC) infusion of increasing doses of the ß₂-AR agonist salbutamol (0.15, 0.3, and 0.6 µg/min) and the endothelial vasodilator acetylcholine (1, 3, and 10 µg/min), we measured (1) changes in lumen diameter (LD) by quantitative coronary angiography in 34 normal, 55 mildly atherosclerotic, and 42 stenotic coronary artery segments and (2) changes in average peak velocity (APV) and coronary blood flow (CBF) with the use of Doppler flow wire in 11 normal, 10 mildly atherosclerotic, and 11 stenotic coronary arteries. In 6 of 11 stenotic coronary arteries, the protocol was repeated after an IC bolus (12 µg/kg) of the -adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 µmol/min) of N^G-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor. Neither salbutamol IC infusion nor acetylcholine significantly changed heart rate or blood pressure, whereas L-NMMA slightly increased blood pressure. In normal coronary arteries, salbutamol increased LD (LD max %: 11±2, P<0.05), APV (APV max %: 53±17, P<0.05), and CBF (CBF max %: 57±17, P<0.05), whereas L-NMMA caused a blunted APV (APV max %: 27±6, P<0.05) and CBF (CBF max %: 29±6, P<0.05) response to salbutamol. In mildly atherosclerotic coronary arteries, the salbutamol increase in LD (LD max %: 10±2, P<0.05), APV (APV max %: 33±12, P<0.05), and CBF (CBF max %: 37±12, P<0.05) was preserved. In stenotic coronary arteries, salbutamol induced a paradoxical reduction in LD (LD max %: –6±2, P<0.05), APV (APV max %: –15±9, P<0.05), and CBF (CBF max %: –15±6, P<0.05), which was no longer observed after phentolamine. Acetylcholine increased LD (LD max %: 14±3, P<0.05), APV (APV max %: 61±20, P<0.05), and CBF (CBF max %: 67±19, P<0.05) in normal coronary arteries. In mildly atherosclerotic coronary arteries, acetylcholine induced a significant reduction in LD (LD max %: –15±2, P<0.05) and no changes in APV (APV max %: –6±13, P=NS) and CBF (CBF max %: –10±13, P=NS). In stenotic coronary arteries, acetylcholine significantly reduced LD (LD max %: –15±3, P<0.05), APV (APV max %: –15±9, P<0.05), and CBF (CBF max %: –15±6, P<0.05).

Conclusions— In severely atherosclerotic coronary arteries, ß₂-adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.

Key Words: receptors, adrenergic, alpha • receptors, adrenergic, beta • atherosclerosis • endothelium • acetylcholine

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