Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit
Journal
British Journal of Pharmacology
Journal Volume
110
Journal Issue
4
Pages
1508-1514
Date Issued
1993
Author(s)
Abstract
The in vivo pharmacological effects of scoparone (6,7?dimethoxycoumarin) in a hyperlipidaemic diabetic rabbit model were investigated. Three groups of rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic?untreated and (3) hyperlipidaemic and diabetic?scoparone treated. The hyperlipidaemic diabetic rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic agent. The plasma levels of total cholesterol, total triglyceride, very low?density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol and high?density lipoprotein (HDL) cholesterol were markedly increased as soon as the rabbit became diabetic at the second week. Scoparone?treatment (5 mg kg?1 day?1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol, 48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol and 79.5% of HDL cholesterol. Six weeks after cholesterol?feeding, the aortic arch and thoracic aorta were dissected for morphological and functional studies. In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was intimal thickening with accumulation of fatty streaks, foam cells and migration of smooth muscle cells to the intima. In the rabbits treated with scoparone, there were fewer pathological morphology changes found in vascular segments than in the untreated hyperlipidaemic diabetic rabbits. In the vascular reactivity experiments, the phenylephrine?induced contraction and nitroprusside?induced dilatation did not differ significantly among the three rabbit groups, except that the contraction was enhanced in the thoracic aorta of hyperlipidaemic diabetic rabbits either untreated or treated with scoparone, as compared to the normal group, and the sensitivity to nitroprusside was increased in the thoracic aorta of the scoparone?treated group as compared to the untreated group. The endothelium?dependent dilatation induced by acetylcholine was significantly attenuated in both the aortic arch and thoracic aorta from the hyperlipidaemic diabetic rabbits as compared to the normal rabbits. This attenuation was partially prevented, when scoparone (5 mg kg?1) was administered daily. These results suggest that scoparone protects against some alterations of plasma lipoproteins, vascular morphology and vascular reactivity in the hyperlipidaemic diabetic rabbit. These protective effects of scoparone may be partly related to its free radical scavenging property. 1993 British Pharmacological Society
SDGs
Other Subjects
acetylcholine; alloxan; cholesterol; high density lipoprotein cholesterol; lipoprotein; low density lipoprotein cholesterol; nitroprusside sodium; phenylephrine; scavenger; scoparone; triacylglycerol; very low density lipoprotein cholesterol; alloxan diabetes mellitus; animal experiment; animal model; animal tissue; aorta arch; article; blood vessel reactivity; cholesterol diet; concentration response; controlled study; histology; hyperlipidemia; lipoprotein blood level; morphology; nonhuman; priority journal; protection; rabbit; subcutaneous drug administration; thoracic aorta; Animal; Antilipemic Agents; Blood Vessels; Coumarins; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Hyperlipidemia; In Vitro; Lipoproteins; Rabbits; Support, Non-U.S. Gov't; Vasodilation
Type
journal article