EFFECTS OF BETA-BLOCKERS ON HMG COA REDUCTASE AND LDL RECEPTOR ACTIVITY IN CULTURED HUMAN SKIN FIBROBLASTS

Previous reports, based on clinical trials and animal experiments, sug gest that beta-blockers may be useful in the prevention of atheroscler osis. Betaxolol, a new beta(1)-selective blocker, was shown to decreas e plasma total and LDL cholesterol levels or to have no adverse effect on those [1-4]. While many reports deal with the metabolism of trigly ceride and high density lipoprotein, fewer publications about choleste rol metabolism are currently available. To clarify the mechanism by wh ich beta-blockers affect lipid metabolism, we examined the effects of beta-blockers on HMG CoA reductase and LDL receptor activity in cultur ed human skin fibroblasts. L-propranolol, a nonselective betablocker, increased HMG CoA reductase activity and decreased LDL receptor activi ty. However, d-propranolol had no major effects on HMG CoA reductase a ctivity. These results suggest that beta-blockers act on PRIG CoA redu ctase through the beta receptors. Beta(1)-blocking action should decre ase HMG CoA reductase activity and increase LDL receptor activity. In fact, betaxolol, a beta(1)-selective blocker, decreased HMG CoA reduct ase activity and increased LDL receptor activity, but metoprolol had n o major effect. We speculate that the discrepancy between betaxolol an d metoprolol in the effect on HMG CoA reductase and the LDL receptor m ight be due to the difference of the extent of beta(1)-selectivity. We conclude that beta(1)-selective blockers are antihypertensive agents potentially valuable in the prevention of atherosclerosis.