Coronary β ₂-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: Novel insights from an in vivo intravascular ultrasound study

Aims The interaction between coronary β2-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 β2-adrenoreceptors, regional plaque burden and segmental endothelial function.Methods and resultsIn 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 doseresponse 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 SLV 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 SLV or CBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a SLV to IC salbutamol (coefficient-0.18, 95 CI-0.32 to-0.044, P = 0.015). ConclusionsIntracoronary 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.