Effects of doxazosin on diet-induced hypercholesterolemia in C57BR/cdJ mice

Plasma cholesterol levels are markedly reduced when doxazosin, a selective alpha 1-adrenoceptor inhibitor, is administered for several days to C57BR/cdJ mice that have been fed a high cholesterol diet. This system affords a useful model for investigating the mechanism by which selective alpha 1-adrenoceptor inhibitors decrease circulating lipid levels. The results indirectly suggest that hypercholesterolemia induced by dietary cholesterol may involve activation of the sympathetic nervous system. The basis for linkage between circulating cholesterol levels and sympathetic nervous activity, while not yet understood, may involve changes in the balance among cholesterol pathways in the liver, alteration of vasomotor tone and control of the activity of vascular endothelial lipases. An additive effect is described for cholestyramine and doxazosin, in which low density lipoprotein cholesterol is decreased by 76% by a combination of maximal doses of the 2 agents.