Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats.
This study examined the influence of hypercholesterolemia on the concentration of plasma immunoreactive (ir) endothelin-1 in rats. Plasma ir-endothelin-1, total cholesterol, triglycerides, and lipoprotein fraction concentrations were measured in three groups of rats; ie, fed a standard diet, a high cholesterol diet, or a high cholesterol diet supplemented with the antihypercholesterolemic drug clinofibrate for 4 and 8 weeks. In the rats fed cholesterol for 8 weeks, morphological changes in thoracic and abdominal aortas were examined. Plasma total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and ir-endothelin-1 concentrations increased significantly in the cholesterol-fed rats after both 4 and 8 weeks. In the clinofibrate-treated rats, these lipid parameters and plasma ir-endothelin-1 levels after 4 and 8 weeks were significantly lower than in the cholesterol-fed rats. The plasma ir-endothelin-1 concentration was correlated with plasma total cholesterol, LDL, and VLDL concentrations in the three study groups after 4 and 8 weeks. Morphologically, neither foam cells formation nor intimal thickening was observed in rats fed the high cholesterol diet for 8 weeks. These observations indicate that hypercholesterolemia without atherosclerosis elevates the plasma ir-endothelin-1 level in rats. The observed increase in plasma ir-endothelin-1 associated with hypercholesterolemia may play a role in the initiation or development of atherosclerotic vascular lesions.
Horio
T
T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Murakawa
K
K
Yasunari
K
K
Yokokawa
K
K
Ueda
M
M
Takeda
T
T
D000818:Animals; D001011:Aorta / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D016232:Endothelins / Q000097:blood* / Q000276:immunology; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D010642:Phenoxyacetates / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
D008076:Cholesterol, HDL; D016232:Endothelins; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010642:Phenoxyacetates; C006231:clinofibrate; D002784:Cholesterol