Decreased membrane fluidity and beta-adrenergic responsiveness in atherosclerotic quail

The effects of increased cholesterol on erythrocyte membrane fluidity and beta-adrenergic function were studied in a quail model of atherosclerosis. Birds fed a cholesterol-supplemented diet developed severe atherosclerosis and hypercholesterolemia after 6 wk. This cholesterol-enriched diet led to a markedly elevated serum cholesterol and a 26% increase in the cholesterol-to-phospholipid ratio in erythrocyte membranes. Electron paramagnetic resonance spectra measured with 5- and 12-doxyl-stearic acid spin-label probes were used to estimate the order of quail erythrocyte membranes. Membrane preparations from cholesterol-fed birds were more highly ordered near the membrane leaflet surface, as well as deeper in the membrane interior, compared with controls. beta-Adrenergic receptor stimulation of adenosine 3',5'-cyclic monophosphate accumulation was blunted in erythrocytes from the hypercholesterolemic quail. There was no change in beta-receptor density or affinity in the cholesterol-enriched membranes. These studies demonstrate that cholesterol incorporation into erythrocyte membranes in vivo is associated with decreased membrane fluidity and decreased beta-adrenergic responsiveness. The atherosclerotic quail may serve as a useful model to further probe the sequelae of hypercholesterolemia on the function of integral membrane proteins.