Beta-adrenoceptors on endothelial cells do not influence release of relaxing factor in dog coronary arteries.

1. The aim of this study was to determine if stimulation of a beta-adrenoceptor on endothelial cells could release an endothelium-derived relaxing factor (EDRF) similar to that released by acetylcholine. 2. In dog coronary rings preconstricted with PGF2 alpha or serotonin, removal of the endothelium did not alter the relaxant responses to isoprenaline. However, in rings preconstricted with the thromboxane-mimetic U46619, removal of the endothelium enhanced the response to isoprenaline. 3. The vasorelaxant responses to isoprenaline in endothelium-denuded rings were inhibited in a concentration-dependent manner by the specific beta 1-adrenoceptor antagonist CGP-20712A (3-100 nmol/l), but were not altered by the beta 2-adrenoceptor antagonist ICI-118551 (30 nmol/l). 4. The vasorelaxant responses to isoprenaline in the presence of CGP-20712A (30 nmol/l) or ICI-118551 (30 nmol/l) were not impaired by removal of the endothelium. 5. Endothelium-dependent vasorelaxant responses to acetylcholine and bradykinin were not altered by isoprenaline (0.1 mumol/l) in the presence of CGP-20712A (30 nmol/l). 6. Therefore, the beta-adrenoceptors on dog coronary artery smooth muscle which produce relaxation are predominantly of the beta 1-subtype. Stimulation of any beta 2-adrenoceptors on the endothelium in dog coronary artery does not release EDRF, and does not modulate endothelium-dependent vasodilatation induced by other agents.