β-ADRENOCEPTORS ON ENDOTHELIAL CELLS DO NOT INFLUENCE RELEASE OF RELAXING FACTOR IN DOG CORONARY ARTERIES

SUMMARY 1. The aim of this study was to determine if stimulation of a β‐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 PGF2α 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 β1‐adrenoceptor antagonist CGP‐20712A (3–100 nmol/l), but were not altered by the β2‐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 μmol/l) in the presence of CGP‐20712A (30 nmol/l). 6. Therefore, the β‐adrenoceptors on dog coronary artery smooth muscle which produce relaxation are predominantly of the β1‐subtype. Stimulation of any β2‐adrenoceptors on the endothelium in dog coronary artery does not release EDRF, and does not modulate endothelium‐dependent vasodilatation induced by other agents.