ATTENUATION OF CYCLOSPORINE-A-INDUCED VASCULAR TOXICITY BY RAMIPRIL

We wished to determine whether chronic inhibition of angiotensin-conve rting enzyme (ACE) prevents the vascular toxicity of cyclosporine A (C x). In aortas isolated from rats treated with ramipril [10 mg/kg/day o rally (p.o.) for 4 weeks], the endothelium-dependent relaxations to ac etylcholine (ACh) were potentiated (the area under the curve (AUC) dec reased from 154 +/- 35 to 63 +/- 12, p < 0.05), but contractions induc ed by phenylephrine (PE) and angiotensin II (AII) were not affected. T herefore, we studied three groups of rats in parallel. Group 1 receive d 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 receive d Cx only (20 mg/kg/day i.m. for 1 week), and group 3 served as contro l. In group 2, ACh-induced relaxations were reduced as compared with t hose of the control group (AUC increased from 141 +/- 34 to 240 +/- 32 , p < 0.05), whereas in group 1, AUC was not significantly different f rom that of group 3 (195 +/- 28 vs. 141 +/- 34). In group 2, PE- and A II-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 AI I were not significantly different from those of group 3. After mechan ical removal of the endothelium, the increased responsiveness to PE an d AII persisted in group 2 whereas AUC values in group 1 were not diff erent 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 i n smooth muscle induced by in vivo exposure to Cx.