beta-Adrenoceptors in endothelium of rabbit coronary artery and alteration in atherosclerosis.

The existence of beta-adrenoceptor (beta-AR) in endothelium of rabbit coronary artery and its alteration in atherosclerosis (AS) were determined by relaxation experiments in isolated preparations and in situ hybridization with a digoxigenin-labelled beta 2-AR cDNA probe. The concentration-relaxing response curves for isoproterenol (ISO) and norepinephrine (NE) in the presence of phentolamine were shifted to the right, and the maximal relaxations were reduced by removing the endothelium. Nitric oxide synthase inhibitor L-NG-nitro-arginine reduced the maximal relaxation induced by ISO, while the cyclooxygenase inhibitor indomethacin showed no effect on relaxation. In situ hybridization showed that mRNA for beta-AR was detected not only in smooth muscles, but also in endothelial cells. Coronary artery AS was created by high cholesterol feeding and was confirmed histologically under light microscopy. The relaxation response to acetylcholine (ACh) was abolished or significantly diminished in AS preparations. The relaxation responses to ISO or NE, however, were potentiated in AS arteries, especially in those which showed diminished (but not abolished) ACh response. The relaxation induced by sodium nitroprusside was reduced significantly in the AS arteries. Those results suggest that beta-AR are present in endothelium of rabbit coronary artery, and that endothelium beta-AR-mediated vasorelaxation is potentiated in AS.