Studies with doxazosin on the saturable binding of 125I-LDL by liver in normocholesterolemic mice.

Tissue culture studies have provided evidence that alpha 1-adrenergic receptor inhibition with doxazosin increases the number of low-density lipoprotein (LDL) receptors in human fibroblasts. A similar effect occurring in vivo might explain the reduction of plasma LDL concentration observed in some clinical trials of prazosin. In order to examine this question further, mice were given doxazosin 100 or 400 micrograms/kg/day by i.p. injection for 4 days, after which they were killed, blood was collected and livers were excised. Binding of 125I-labelled human LDL to tissue homogenates, over the concentration range 30-120 micrograms LDL protein/ml, was measured at 37 degrees C in the absence and presence of excess unlabelled LDL. Woolf plots of the results for saturable binding were found to be compatible with a single class of binding site. In control animals Bmax for this receptor was 867 +/- 117 ng LDL protein/mg tissue protein, and the equilibrium dissociation constant was 32.7 +/- 6.6 micrograms LDL protein/ml (mean +/- SD, n = 5). Doxazosin treatment had no effect on either parameter of 125I-LDL binding. A trend towards a decrease in liver triglyceride concentration with increasing doses of doxazosin was recorded, but there was no evidence for effects on liver cholesterol or serum lipid concentrations.