title: Role of beta2 adrenergic receptors in human atherosclerotic coronary arteries.
abstract: BACKGROUND
  Adrenergic regulation of coronary vasomotion is balanced between alpha1-adrenergic-mediated (alpha1-AR) constriction and beta2-adrenergic-mediated (beta2-AR) relaxation. This study aimed at assessing the role of beta2-ARs in normal, mildly atherosclerotic, and stenotic human coronary arteries.
  
  
  RESULTS
  During intracoronary (IC) infusion of increasing doses of the beta2-AR agonist salbutamol (0.15, 0.3, and 0.6 mug/min) and the endothelial vasodilator acetylcholine (1, 3, and 10 microg/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 microg/kg) of the alpha-adrenergic blocker phentolamine. In 6 of 11 normal coronary arteries, the protocol was repeated after an IC infusion (60 micromol/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, beta2-adrenergic vasodilatation is impaired, and this might contribute to alter the vasomotor balance, further precipitating myocardial ischemia during sympathetic activation.
authors.affiliation: Division of Cardiology, Federico II University of Naples, Italy. emanuele.barbato@uniroma1.it
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
authors.forename: Federico
authors.initials: F
authors.lastname: Piscione
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Gennaro
authors.initials: G
authors.lastname: Galasso
authors.forename: Plinio
authors.initials: P
authors.lastname: Cirillo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
authors.forename: William
authors.initials: W
authors.lastname: Wijns
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000420:Albuterol / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000503:physiopathology; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009574:Nitro Compounds / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D009574:Nitro Compounds; D018343:Receptors, Adrenergic, beta-2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D000420:Albuterol; D010646:Phentolamine