Effects of reserpine on expression of the LDL receptor in liver and on plasma and tissue lipids, low density lipoprotein and fibrinogen in rabbits in vivo.
The effects of administering reserpine (0.1 mg/kg) or 17alpha-ethinyloestradiol (2.5 mg/kg) to New Zealand White rabbits on low density lipoprotein receptors in liver, on plasma low density lipoprotein and fibrinogen and on plasma and tissue lipids were determined. Blood pressure and heart rate were also followed. The drugs were injected subcutaneously into conscious unrestrained rabbits for 5 days. On the 6th day homologous 125I-tyramine cellobiose labelled low density lipoprotein (125I-TC-LDL) was injected intravenously and 24 h later the animals were killed. Compared to controls, reserpine significantly increased LDL receptor expression in the liver by about threefold, and reduced total cholesterol in plasma, aorta and heart, without affecting plasma triglycerides. The reductions in plasma cholesterol and heart were due to decreases in both unesterified and esterified cholesterol. Similar effects were observed with oestrogen, except that there was no change 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 accelerated the plasma clearance of intravenously injected homologous 125I-TC-LDL and reduced its accumulation in aortic wall. Neither reserpine nor oestradiol affected blood pressure, haematocrit or plasma fibrinogen. The results suggest that reserpine is an affective anti-atherogenic drug capable of decreasing cholesterol in plasma, arteries and heart by increasing high affinity LDL receptors in the liver.
Shafi
S
S
Pathopharmacology Unit, The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK. s.shafi@mds.qmw.ac.uk
Stepanova
I P
IP
Fitzsimmons
C
C
Bowyer
D E
DE
Welzel
D
D
Born
G V
GV
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D046508:Culture Techniques; D004195:Disease Models, Animal; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005340:Fibrinogen / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007279:Injections, Subcutaneous; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000097:blood / Q000187:drug effects*; D012016:Reference Values; D012110:Reserpine / Q000008:administration & dosage*; D012680:Sensitivity and Specificity
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D004997:Ethinyl Estradiol; D012110:Reserpine; D005340:Fibrinogen