Endothelial modulation of β-adrenergic dilation of large coronary arteries in conscious dogs

• Published in: Circulation (New York, N.Y.) Vol. 92; no. 9; pp. 2627 - 2635
• Main Authors: BIJAN GHALEH, BEA, M.-L, DUBOIS-RANDE, J.-L, GIUDICELLI, J.-F, HITTINGER, L, BERDEAUX, A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.11.1995
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Atenolol - pharmacology; Biological and medical sciences; Coronary Vessels - drug effects; Coronary Vessels - physiology; Dogs; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Heart; Isoproterenol - pharmacology; Male; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; Vasodilation - drug effects; Vasodilation - physiology; Vertebrates: cardiovascular system; Fissipedia; Carnivora; Vertebrata; Mammalia; Coronary artery; Exploration; Circulatory system; Hemodynamics; Dog; Endothelium; β-Adrenergic receptor
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.92.9.2627

Endothelium-derived relaxing factors have been described as important intermediates in beta-adrenergic vasodilation of resistance coronary vessels, but their involvement at the level of large epicardial coronary arteries remains controversial. Therefore, we examined the role of vascular endothelium in the beta-adrenergic-mediated vasodilation of large epicardial coronary arteries in conscious dogs. Nine dogs were instrumented for measurement of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary blood flow velocity (CBFv) with a Doppler technique in response to graded doses of isoproterenol (0.001 to 0.1 microgram/kg IV bolus). Under control conditions, isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept constant at its baseline value by inflation of a cuff occluder, isoproterenol still induced dose-dependent increases in CD, but the latter were of lesser magnitude than those observed under normal CBFv conditions (110 +/- 20 versus 170 +/- 30 microns, respectively, ie, a reduction of 33% of the dilatory response at 0.1 microgram/kg, P < .01). In the same dogs, the coronary endothelium was then mechanically removed at the site of CD measurement by a balloon angioplasty technique. After this procedure, the dose-dependent increases in CD induced by isoproterenol under either normal or controlled CBFv conditions were overimposable, and their magnitude was similar to that of the increases observed in the presence of an intact endothelium when CBFv was kept constant. After beta 1-adrenergic receptor blockade by atenolol (1 mg/kg), isoproterenol-induced increases in CD were abolished either when CBFv was kept constant or after endothelium removal. In conscious dogs, the direct stimulating effect of isoproterenol on beta 1-adrenergic receptors is endothelium-independent at the level of large coronary arteries. The endothelium reinforces the dilatory response to isoproterenol through an indirect, flow-dependent mechanism.