Effect of simvastatin therapy on blood and tissue ATP levels and erythrocyte membrane lipid composition

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors decrea se mevalonate and subsequently cholesterol synthesis competitively. Mevalon ate is also the precursor of ubiquinone. Ubiquinone is an important compone nt of electron transport chain. We therefore investigated the effect of sim vastatin on rat blood and tissue ATP concentrations and the lipid compositi on of red blood cell membranes after 4 weeks of therapy. Significant reduct ions in rat plasma cholesterol, triglyceride, and blood ATP concentrations were detected. Tissue ATP levels were not affected. Membrane phospholipids increased, while cholesterol and the cholesterol to phospholipid ratio decr eased (P<0.05). A positive correlation between the plasma cholesterol conce ntration and the cholesterol to phospholipid ratio was noted (P<0.05, r=0.8 51). Our results show that HMG-CoA reductase inhibitors change the composit ion and probably also the functions of cell membrane lipids and blood ATP c oncentration.