Role of β ₂ Adrenergic Receptors in Human Atherosclerotic Coronary Arteries

Abstract

Background-Adrenergic regulation of coronary vasomotion is balanced between ␣ 1 -adrenergic-mediated (␣ 1 -AR) constriction and ␤ 2 -adrenergic-mediated (␤ 2 -AR) relaxation. This study aimed at assessing the role of ␤ 2 -ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries. Methods and Results-During intracoronary (IC) infusion of increasing doses of the ␤ 2 -AR agonist salbutamol (0.15, 0.3, and 0.6 g/min) and the endothelial vasodilator acetylcholine (1, 3, and 10 g/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 g/kg) of the ␣-adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 mol/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 %: 11Ϯ2, PϽ0.05), APV (APV max %: 53Ϯ17, PϽ0.05), and CBF (CBF max %: 57Ϯ17, PϽ0.05), whereas L-NMMA caused a blunted APV (APV max %: 27Ϯ6, PϽ0.05) and CBF (CBF max %: 29Ϯ6, PϽ0.05) response to salbutamol. In mildly atherosclerotic coronary arteries, the salbutamol increase in LD (LD max %: 10Ϯ2, PϽ0.05), APV (APV max %: 33Ϯ12, PϽ0.05), and CBF (CBF max %: 37Ϯ12, PϽ0.05) was preserved. In stenotic coronary arteries, salbutamol induced a paradoxical reduction in LD (LD max %: Ϫ6Ϯ2, PϽ0.05), APV (APV max %: Ϫ15Ϯ9, PϽ0.05), and CBF (CBF max %: Ϫ15Ϯ6, PϽ0.05), which was no longer observed after phentolamine. Acetylcholine increased LD (LD max %: 14Ϯ3, PϽ0.05), APV (APV max %: 61Ϯ20, PϽ0.05), and CBF (CBF max %: 67Ϯ19, PϽ0.05) in normal coronary arteries. In mildly atherosclerotic coronary arteries, acetylcholine induced a significant reduction in LD (LD max %: Ϫ15Ϯ2, PϽ0.05) and no changes in APV (APV max %: Ϫ6Ϯ13, PϭNS) and CBF (CBF max %: Ϫ10Ϯ13, PϭNS). In stenotic coronary arteries, acetylcholine significantly reduced LD (LD max %: Ϫ15Ϯ3, PϽ0.05), APV (APV max %: Ϫ15Ϯ9, PϽ0.05), and CBF (CBF max %: Ϫ15Ϯ6, PϽ0.05). Conclusions-In severely atherosclerotic coronary arteries, ␤ 2 -adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.

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