Effect of reserpine treatment on low-density lipoproteins in arterial wall and internal organs of rats.
The effects were determined in rats of single injections of reserpine at increasing doses (0.5, 1.58, and 5.0 mg/kg) on low-density lipoprotein (LDL) and cholesterol in aortic wall, heart, liver, kidney, and adrenal gland. Catecholamine levels in plasma, heart, and liver, arterial blood pressure, and heart rate were also monitored. Reserpine was injected intraperitoneally, followed immediately by the administration of [3H]cholesterol by gavage. Twelve hours later, homologous 125I-tyramine cellobiose-labeled LDL (125I-TC-LDL) was injected intravenously. Twenty-four hours later, the rats were killed, and the radioactivities of aortic walls, heart, liver, kidney, and adrenal glands were determined. The results showed that after reserpine treatment the accumulation of both the 125I-TC label derived from LDL and total [3H]cholesterol was significantly reduced in aortic wall and heart, increased in liver, and unchanged in the kidney and adrenal gland. At higher doses (1.58 and 5.0 mg/kg), reserpine significantly accelerated the plasma clearance of radiolabelled LDL. Plasma noradrenaline in reserpine-treated animals decreased maximally (86%) by 12 h and by 61-71% at 36 h compared with the control. Plasma adrenaline increased transiently after injection of reserpine and then returned to the basal levels. Reserpine greatly decreased noradrenaline and adrenaline levels in heart and liver. Arterial blood pressure was decreased significantly (0.001 < p < 0.05) at 12 h by the two lower doses of reserpine and then returned to normal values over the next 24 h. The results indicate that reserpine decreases LDL cholesterol in artery wall and heart and increases it in liver. These findings suggest that reserpine could find a new use as a cholesterol-lowering drug for the prevention of atherosclerosis.
Shafi
S
S
Pathopharmacology Unit, The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, England. S.Shafi@mds.qmw.ac.uk
Welzel
D
D
Weidinger
G
G
Brown
J
J
Born
G V
GV
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001161:Arteriosclerosis / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D012110:Reserpine; D002784:Cholesterol; D009638:Norepinephrine; D004837:Epinephrine