Intimal hyperplasia, smooth muscle cell migration and proliferation with the formation of extracellular matrix, is a frequent cause of failure of vascular surgery and angioplasty.
Local angiotensin II effects in the artery wall may participate in regulation of the vascular response to arterial injury, apparently independent of the plasma renin and angiotensin system. This is supported by the observation that angiotensin
converting enzyme (ACE) inhibitors have been shown to block intimalhyperplasia after arterial injury in the rat.
This examination was intiated to prove that previous observations with use of ACE inbibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, and we tested the ability of an unrelated drug, auticoagulant
heparin,
to
similarly block intimal hyperplasia induced by aortic injury in the rat. We also investingate if the synertic effect is to be seen when ramipril and heparin were given togenther.
Balloon catheter aortic denudation was performed in 25 rats pharmacologically treated from 6 days before to 14 days after surgery and split into four groups: group A(control group), normal feeding ; group B(ramipril(r) group), ramipril(r)
10mg/kg/day
orally ; group C(heparin group), heparin 1200 u/kg/day subcutaneously ; group D(combined group), both ramipril(r) and heparin.
Animals were killed and aortas were perfused and fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to media ratios(I-M ratio) were calculated by image analyzed system.
@ES The results were as follows :
@EN 1) Marked intimal thickening with a mean I-M ratio of 95.1±2.76% in the control group. In contrast, the I-M ratio in the ramipril group were reduced to 37.3±2.06% (P=0.0001), heparin group 29.7±1.58%(P=0.0001), and combined group
16.6±1.3%
significantly.
2) Blood pressure in ramipril group decreased from 111.7±5.16 mmHg to 95.8±5.84 mmHg (P=0.0001) and in combined group from 111.7±6.06mmHg to 92.5±5.24mmHg after 6 days, whereas heparin had no effect on blood pressure (114.2±8.6 mmHg to
111.7±6.06
mmHg).
This study shows that attenuating the angiotensin system at the level of production reduces the intimal hyperplasia induced by oartic injury. These results further support the hypothesis that angiotensin II induces smooth muscle cell prolifertion
and
that the heparin also block the intimal hyperplasia by inhibiting smooth muscle cell proliferation independant of anticoagulation after aortic injury in the rat.
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