Effects of diazepam (Valium) on aortic atherogenesis and plasma lecithin: cholesterol acyltransferase activity in cockerels fed an atherogenic diet.

Blood plasma LCAT (lecithin: cholesterol acyltransferase, EC 2.3.1.43) was studied in cockerels fed an atherogenic diet to determine if attenuation of aortic atherogenesis, as a result of simultaneous treatment of the birds with diazepam, might be related to modulation of enzyme activity by the drug. Administration of diazepam (0.6 mg/kg) did not influence LCAT. It was observed that no relationship could be established between enzyme activity and the extent of aortic atherogenesis. In contrast, addition of diazepam in vitro to cockerel plasma caused a concentration-dependent inhibition of LCAT activity. The effect was most pronounced when diazepam was present at a concentration of 50-200 microM, where inhibition of enzyme activity was 25-65%. Thus, pharmacologic doses of diazepam do not appear to affect LCAT in vivo. It is concluded that diazepam attenuates aortic atherogenesis in cockerels fed an atherogenic diet by a mechanism independent of LCAT.