Comparison of the antiatherogenic effects of isradipine and ramipril in cholesterol-fed rabbits: I. Effect on progression of atherosclerosis and endothelial dysfunction.
This study was designed to compare the effects of a calcium antagonist (isradipine) and a converting enzyme inhibitor (ramipril) on progression and regression of atherosclerosis in hypercholesterolemic rabbits. Sixty rabbits in three groups were fed a 0.3% cholesterol diet for 4 weeks. After this induction period, group II received the 0.3% cholesterol diet, group III received cholesterol diet with isradipine (0.33 mg/kg/day), and group IV received cholesterol with ramipril (0.33 mg/kg/day) for 12 more weeks. A group of 20 rabbits received a standard diet throughout the study (group I). After 16 weeks, 10 rabbits were randomly chosen from each group and used in the progression study. The other rabbits were placed on a standard diet and remained on their respective drug regimen for 12 more weeks. In the progression phase of the study, ramipril significantly attenuated the percentage of aortic lesions in group IV (35 +/- 6%) as compared with group II (56 +/- 6%, p < 0.05), whereas isradipine had no effect. Acetylcholine (ACh)-induced maximum endothelium-dependent relaxations (EDR) of aortic rings were significantly reduced by the atherogenic diet to 37 +/- 4 versus 77 +/- 2% in group I (p < 0.05). Treatment with ramipril significantly improved maximum EDR to 53 +/- 3% (p < 0.05 vs. group II). Isradipine had no significant effect on impaired EDR. Aortic rings with endothelium from group II developed supersensitivity to sodium nitroprusside (SNP) and had significantly reduced basal cyclic GMP levels as compared with those of group I. Both drugs prevented development of supersensitivity to SNP and blunted the cholesterol-induced reduction in basal cyclic GMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Riezebos
J
J
Department of Pharmacotherapy, University of Utrecht, The Netherlands.
Vleeming
W
W
Beems
R B
RB
van Amsterdam
J G
JG
Meijer
G W
GW
de Wildt
D J
DJ
Porsius
A J
AJ
Wemer
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D017275:Isradipine / Q000627:therapeutic use*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D011817:Rabbits; D017257:Ramipril / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D002791:Cholesterol, Dietary; D010743:Phospholipids; D014280:Triglycerides; D009599:Nitroprusside; D002784:Cholesterol; D000242:Cyclic AMP; D017257:Ramipril; D017275:Isradipine