Inhibitory effect of the new calcium antagonist AJ-2615 on progression of atherosclerosis in cholesterol-fed rabbits.
The effects of a new calcium antagonist, AJ-2615, on progression of atherosclerosis were investigated in rabbits fed a diet high in cholesterol and compared with those of prazosin, diltiazem, and their combination. In the AJ-2615 (30 mg/kg p.o. once daily) group, high cholesterol diet-induced increases in plasma concentrations of total cholesterol, free cholesterol, and phospholipid were significantly decreased. In addition, increases in aortic lipids and calcium content, as well as those in the atherosclerotic lesion area were clearly reduced by AJ-2615. On the other hand, prazosin (3 mg/kg p.o. twice daily) and diltiazem (50 mg/kg p.o. twice daily) groups displayed no such inhibitory effects. However, the group receiving the combination of prazosin and diltiazem at their respective dose levels exhibited a significant reduction in the increase in calcium content of the aorta and a slight decrease in the atherosclerotic lesion area, although there was no decrease in plasma or aortic lipid content. These results suggest that in addition to its calcium antagonistic and alpha 1-adrenoceptor blocking actions, some other yet-unidentified properties of AJ-2615 might contribute to the antiatherosclerotic effect of this agent.
Minato
H
H
Department of Pharmacology, Dainippon Pharmaceutical Company, Osaka, Japan.
Ikeno
A
A
Yamada
T
T
Kato
H
H
Zushi
K
K
Kurokawa
M
M
Masuda
Y
Y
Hosoki
K
K
Karasawa
T
T
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002791:Cholesterol, Dietary / Q000097:blood / Q000633:toxicity*; D003988:Dibenzothiepins / Q000627:therapeutic use*; D004110:Diltiazem / Q000627:therapeutic use; D008297:Male; D010743:Phospholipids / Q000097:blood; D010879:Piperazines / Q000627:therapeutic use; D011224:Prazosin / Q000627:therapeutic use; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D002121:Calcium Channel Blockers; D002791:Cholesterol, Dietary; D003988:Dibenzothiepins; D010743:Phospholipids; D010879:Piperazines; D014280:Triglycerides; D004110:Diltiazem; C067818:monatepil; D011224:Prazosin