Comparative study of the effect of beta-blockers with different pharmacological properties on cholesteryl ester formation in mouse peritoneal macrophages.
The effect of three beta-blockers: non-selective (propranolol), beta 1-selective (metoprolol), and with intrinsic sympathomimetic activity (pindolol), was investigated on 14C-oleic acid incorporation into cholesteryl esters in mouse peritoneal macrophages. Incorporation of 14C-oleic acid into cholesteryl esters was reduced about 10-fold by propranolol at 10(-4) M while incorporation into triacylglycerols was only 30% decreased at the same concentration. Metoprolol and pindolol had no significant effect on 14C-oleic incorporation into cholesteryl esters or triacylglycerols. Finally, propranolol inhibited the acyl-coenzyme A: cholesterol-O-acyltransferase activity, measured in vitro on macrophages homogenates, while the other studied beta-blockers were ineffective. These results suggest that propranolol could antagonize cholesteryl ester accumulation by macrophages, one of the main processes involved in atherogenesis.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002788:Cholesterol Esters / Q000096:biosynthesis*; D005260:Female; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D014280:Triglycerides / Q000096:biosynthesis
D000319:Adrenergic beta-Antagonists; D002788:Cholesterol Esters; D009829:Oleic Acids; D014280:Triglycerides; D019301:Oleic Acid; D011433:Propranolol; D010869:Pindolol; D002785:Sterol O-Acyltransferase; D008790:Metoprolol