Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats.
1. The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2. In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3. Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4. In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5. The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg-1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6. In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved. Dicentrine therapy caused significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction in hyperlipidaemic rats. However, dicentrine neither prevented the impaired relaxation to acetylcholine, nor affected the relaxation to nitroprusside during atherosclerosis progression.7. It is concluded that dicentrine decreases MAP, plasma CE, LDL-CE, plasma TG, VLDL-TG,vascular hyperreactivity to phenylephrine and increases HDL-CE levels. Dicentrine may thus hold potential for the reduction of two of the major risk factors, hypertension and hyperlipidaemia, for cardiovascular disease.
Yu
S M
SM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Kang
Y F
YF
Chen
C C
CC
Teng
C M
CM
D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D001158:Arteries / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006949:Hyperlipidemias / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014280:Triglycerides / Q000097:blood
D001060:Aporphines; D002791:Cholesterol, Dietary; D008055:Lipids; D008074:Lipoproteins; D010975:Platelet Aggregation Inhibitors; D014280:Triglycerides; D002784:Cholesterol; C067342:dicentrine