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(Circulation. 1995;92:2627-2635.)
© 1995 American Heart Association, Inc.

Articles

Endothelial Modulation of ß-Adrenergic Dilation of Large Coronary Arteries in Conscious Dogs

Bijan Ghaleh, PhD; Marie-Luce Béa, PhD; Jean-Luc Dubois-Randé, MD; Jean-François Giudicelli, MD; Luc Hittinger, MD; Alain Berdeaux, MD

From the Département de Pharmacologie, Faculté de Médecine Paris-Sud (B.G., M-L.B., J.F.G., A.B.), the Service de Cardiologie (J.L.D.R.), and the Institut National de la Santé et de la Recherche Médicale (L.H.) U400, Hôpital Henri Mondor, Créteil, France.

Correspondence to Pr J.F. Giudicelli, Département de Pharmacologie, Faculté de Médecine Paris-Sud, 63, rue Gabriel Péri, 94276 Le Kremlin Bicêtre Cédex, France.

Background Endothelium-derived relaxing factors have been described as important intermediates in ß-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 ß-adrenergic–mediated vasodilation of large epicardial coronary arteries in conscious dogs.

Methods and Results 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 µg/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 µm, respectively, ie, a reduction of 33% of the dilatory response at 0.1 µg/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 ß₁-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.

Conclusions In conscious dogs, the direct stimulating effect of isoproterenol on ß₁-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.

Key Words: endothelium-derived factors • receptors, adrenergic, beta • vasodilation

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