ATTENUATION OF CYCLOSPORINE-A-INDUCED VASCULAR TOXICITY BY RAMIPRIL

被引:6
作者
BERKENBOOM, G
BREKINE, D
UNGER, P
GULBIS, B
FONTAINE, J
机构
[1] FREE UNIV BRUSSELS, HOP ERASME, DEPT CLIN CHEM, B-1070 BRUSSELS, BELGIUM
[2] FREE UNIV BRUSSELS, INST PHARM, DEPT PHARMACOL, B-1050 BRUSSELS, BELGIUM
关键词
CYCLOSPORINE A; RAMIPRIL; RAT AORTA;
D O I
10.1097/00005344-199407000-00004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We wished to determine whether chronic inhibition of angiotensin-converting enzyme (ACE) prevents the vascular toxicity of cyclosporine A (Cx). In aortas isolated from rats treated with ramipril [10 mg/kg/day orally (p.o.) for 4 weeks], the endothelium-dependent relaxations to acetylcholine (ACh) were potentiated (the area under the curve (AUC) decreased from 154 +/- 35 to 63 +/- 12, p < 0.05), but contractions induced by phenylephrine (PE) and angiotensin II (AII) were not affected. Therefore, we studied three groups of rats in parallel. Group 1 received ramipril 10 mg/kg/day p.o. for 4 weeks and ramipril 10 mg/kg/day p.o. plus Cx 20 mg/kg/day intramuscularly, in fifth week; group 2 received Cx only (20 mg/kg/day i.m. for 1 week), and group 3 served as control. In group 2, ACh-induced relaxations were reduced as compared with those of the control group (AUC increased from 141 +/- 34 to 240 +/- 32, p < 0.05), whereas in group 1, AUC was not significantly different from that of group 3 (195 +/- 28 vs. 141 +/- 34). In group 2, PE- and AII-induced contractions were enhanced; AUC values for PE and AII were 495 +/- 45 versus 348 +/- 38 in group 3 and 424 +/- 28 versus 314 +/- 17 in group 3, respectively (p < 0.05). In group 1, AUCs for PE and AII were not significantly different from those of group 3. After mechanical removal of the endothelium, the increased responsiveness to PE and AII persisted in group 2 whereas AUC values in group 1 were not different from those of group 3. Blood pressure (BP) and plasma creatinine level were similar in the three groups. Thus, chronic ACE inhibition may attenuate the endothelial dysfunction and the functional changes in smooth muscle induced by in vivo exposure to Cx.
引用
收藏
页码:17 / 21
页数:5
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