| Objective: Angiotensin II (Ang II) plays a critic role in cardiovascular disease and has been implicated in the development of restenosis after iatrogenic vascular injury through several pathophysiologic mechanisms. In this study, we used a rabbit abdominal atery balloon-injured model to study the effect of angiotensin coverting enzyme inhibitor(ACEI) in restenosis.Methods: Twenty-Four male New Zealand white rabbits, mean weight 1.99±0.12Kg, were divided into three groups randomly. Twenty rabbits were received abdominal artery balloon-injury, four rabbits as control. After balloon-injury, one group(n=10) were received angiotensin-coverting enzyme inhibitor(Fosinopril sodium, 12.5mg/Kg.d) and the other group(n=10) were received diuretic(DHCT, 6.25mg/Kg.d), control were received neither abdominal artery balloon-injury nor any administration.Results: Control(n=4), DHCT group(n=8) and ACEI group(n=10) have completed the study. Four weeks after administration, the systolic pressure among three groups have no difference but the diastolic pressure of ACEI group and DHCT group show a significantly lower compared to control (ACEI group 67±9 vs 75±6mmHg, p<0.05, DHCT group 63 + 10 vs 75±6mmHg, p<0.05). There was no significance in both systolic pressure and diastolic pressure between ACEI group and ACEI group(systolic pressure 115 + 11 vs 118 + 10mmHg, p>0.05, diastolic pressure 63 + 10 vs 67 + 9mmHg, p>0.05). Computer-assisted morphometric analysis revealed that the neointimal area was 0 in control. But there was a significant reduction in the neointimal area in ACEI group compared to DHCT group(0.29±0.08 vs 0.86 ± 0.15mm2, p<0.01). The luman area was significantly lower in DHCT group compared to ACEI group(2.5+0.28 vs 3.3+0.20mm2, p<0.01) and control(1.6±0.18 vs 3.5 ±0.13 mm2, PO.01), there was no difference between ACEI group and control(3.3± 0.20 vs 3.5 ±0.13mm2, P>0.05). Using a ELISA method, there was no change in the plasma concentration of HGF among three groups(491±86 vs 485 ±84 vs 507 ± 106pg/ml, p>0.05). The concentration of vascular tissue HGF in control and ACEI group was significantly higher compared to DHCT group(49.2±4.6 vs 37.4±6.3ng/g, p<0.05; 47.6 + 5.24 vs 37.4±6.28ng/g.tissue, p<0.05), but showed no difference between control and ACEI group(49.2±4.6 vs 47.6±5.24ng/g, p<0.05). The higher concentration of local HGF was negative correlation to the reduction of neointimal area(r=-0.75, p<0.01), there was no correlation between concentration of plasma HGF and neointimal area(r=0.02, p=NS).Conclusions: The present study demonstrated that ACEI significantly inhibited neointimal formation and accompanied with a significant increase of local vascular HGF in rabbit abdominal artery after balloon-injury. We also founded a negative correlation between tissue HGF concentration and intimal area and no correlation between plasma HGF and neointimal formation. Overall, in addition to its direct effect, partly, ACEI reducing restenosis might be due to increase of local vascular HGF through enhancement of reendothelialization after balloon-injury and depend on an autocrine-paracrine manner.
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