title: Coronary β2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.
abstract: OBJECTIVE
  The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function.
  
  
  RESULTS
  In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.
authors.affiliation: Discipline of Medicine,  University of Adelaide, Adelaide, South Australia,  Australia.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.forename: Gary Y H
authors.initials: GY
authors.lastname: Liew
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.forename: Darryl P
authors.initials: DP
authors.lastname: Leong
authors.forename: Angelo
authors.initials: A
authors.lastname: Carbone
authors.forename: Barbara
authors.initials: B
authors.lastname: Copus
authors.forename: Dennis T L
authors.initials: DT
authors.lastname: Wong
authors.forename: John F
authors.initials: JF
authors.lastname: Beltrame
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Worthley
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Worthley
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017566:Microvascular Angina / Q000209:etiology / Q000503:physiopathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D015588:Observer Variation; D058226:Plaque, Atherosclerotic / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D018084:Ultrasonography, Interventional / Q000009:adverse effects / Q000379:methods; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000420:Albuterol