Role of β2 adrenergic receptors in human atherosclerotic coronary arteries

Background - Adrenergic regulation of coronary vasomotion is balanced between alpha(1)-adrenergic-mediated (alpha(1)-AR) constriction and beta(2)-adrenergic-mediated (beta(2)-AR) relaxation. This study aimed at assessing the role of beta(2)-ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries. Methods and Results - During intracoronary (IC) infusion of increasing doses of the beta(2)-AR agonist salbutamol (0.15, 0.3, and 0.6 mug/min) and the endothelial vasodilator acetylcholine ( 1, 3, and 10 mug/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 mug/kg) of the alpha-adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 mumol/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, beta(2)-adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.