Long-term low-dose treatment with reserpine of cholesterol-fed rabbits reduces cholesterol in plasma, non-high density lipoproteins and arterial walls.
The effects of long-term low-dose treatment with reserpine on plasma lipoproteins and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low-density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys; plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine at 43 microg/kg. d was continuously infused subcutaneously via implanted minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine (n = 4) significantly reduced the elevated levels of plasma total cholesterol and esterified and unesterified cholesterol throughout the study, and at 6 weeks of treatment these reductions were 42, 41, and 49%, respectively. The increased cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was reduced by 73% (p < 0.004) and 125I-tyramine cellobiose-labeled LDL by 67 to 86% (0.05 < p <0.004), respectively. The aortic intimal-medial thickness ratio was reduced by 70%. The decrease in elevated plasma total cholesterol was mainly due to cholesterol reductions in both LDL (41%) and non-high density lipoprotein (HDL) of density < 1.019 g/ml (51%). HDL cholesterol and triglyceride levels were unchanged. Reserpine had no significant effects on the clearance of 125I-tyramine cellobiose-LDL from plasma and there was a trend towards an increase in hepatic LDL receptor expression. Heart rate was decreased by 28%. There were no significant effects on blood pressure, liver and heart lipids, hematocrit, or plasma fibrinogen. The results suggest that treatment of cholesterol-fed rabbits with reserpine at a low dose over a long period prevents increases in plasma atherogenic lipoproteins. Reserpine decreases the cholesterol in aortic walls and the intima-media thickness ratio. This anti-atherosclerotic effect of reserpine may have therapeutic implication.
Shafi
Shahida
S
Pathopharmacology Unit, The William Harvey Research Institute, St. Bartholomew's, and the Royal London School of Medicine and Dentistry, London, UK. S.SHAFI@mds.qmw.ac.uk
Stepanova
Irina P
IP
Fitzsimmons
Colin
C
Bowyer
David E
DE
Born
Gustav V R
GV
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012110:Reserpine / Q000008:administration & dosage*
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D011973:Receptors, LDL; D012110:Reserpine; D002784:Cholesterol