Effects of reserpine on expression of the LDL receptor in liver and on plasma and tissue lipids, low density lipoprotein and fibrinogen in rabbits invivo

The effects of administering reserpine (0.1 mg/kg) or 17 alpha-ethinyloestr adiol (2.5 mg/kg) to New Zealand White rabbits on low density lipoprotein r eceptors in liver, on plasma low density lipoprotein and fibrinogen and on plasma and tissue lipids were determined. Blood pressure and heart rate wer e also followed. The drugs were injected subcutaneously into conscious unre strained rabbits for 5 days. On the 6th day homologous I-125-tyramine cello biose labelled low density lipoprotein (I-125-TC-LDL) was injected intraven ously and 24 h later the animals were killed. Compared to controls, reserpi ne significantly increased LDL receptor expression in the liver by about th reefold, and reduced total cholesterol in plasma, aorta and heart, without affecting plasma triglycerides. The reductions in plasma cholesterol and he art were due to decreases in both unesterified and esterified cholesterol. Similar effects were observed with oestrogen, except that there was no chan ge in esterified cholesterol in aorta. In liver, a decrease of 24% in total cholesterol was due mainly to decreased esterified cholesterol. In adrenal glands total cholesterol increased by 25%. Reserpine significantly acceler ated the plasma clearance of intravenously injected homologous I-125-TC-LDL and reduced its accumulation in aortic wall. Neither reserpine nor oestrad iol affected blood pressure, haematocrit or plasma fibrinogen. The results suggest that reserpine is an affective anti-atherogenic drug capable of dec reasing cholesterol in plasma, arteries and heart by increasing high affini ty LDL receptors in the liver. (C) 2000 Elsevier Science Ireland Ltd. All r ights reserved.