Search

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.

We studied the effects of psychosocial stress (S) and diazepam (D) on plasma lipids, adrenocorticotropin (ACTH), and corticosterone (B) levels of cockerels fed an atherogenic diet (AD) consisting of 2% cholesterol plus 5% cottonseed oil added to plain mash (PM). Seventy-six eight-week-old DeKalb cockerels were randomly assigned to the following groups: I. PM; II. PM + D; III. PM + S; ;IV. PM + S + D; V. AD; VI. AD + D; VII. AD + S and VIII. AD + S + D. S was induced by housing two birds to a cage and pairing them to a different bird daily. D was administered daily by gavage. Plasma ACTH and B levels were analyzed by RIA. Aortic atherosclerosis was grossly graded on a scale of 0-4 and also by gravimetric planimetry. After 10 weeks: 1. S birds had a significantly higher incidence and severity (p less than 0.04) of aortic atherogenesis and elevated ACTH and B levels (p less than 0.001) compared to unstressed PM groups. 2. AD significantly elevated the plasma levels of cholesterol, triglycerides, and the lipoprotein cholesterol that was precipitated by heparin-manganese (LDL-C + VLDL-C), compared to initial and/or PM levels (p less than 0.001). AD birds had a greater incidence and more severe aortic lesions in comparison to PM groups (p less than 0.002). Plasma hormone levels were significantly lower in birds fed AD alone compared to controls and stressed birds. 3. D significantly reduced the severity of aortic atheroma as well as decreased hormone levels in all treated groups (p less than 0.001). Therefore, we conclude that aortic atherosclerosis in cockerels can be induced by S and/or AD, and D can markedly reduce atherogenesis under these conditions. Since both AD and D decreased plasma ACTH and B levels, the anti-atherogenic action of D in these birds does not seem to directly involve these pituitary-adrenocortical hormones.