Miyazaki M, Wada T, Shiota N, Takai S
Department of Pharmacology, Osaka Medical College, Takatsuki-City, Japan.
J Hum Hypertens. 1999 Jan;13 Suppl 1:S21-5; discussion S33-4. doi: 10.1038/sj.jhh.1000745.
The roles of angiotensin (Ang) II as produced by two different enzymes, angiotensin-converting enzyme (ACE) and chymase, were investigated in a canine experimental model where intima hyperplasia was induced by balloon catheterization in the common carotid and femoral arteries. The animals received oral candesartan cilexetil (3 mg/kg) or enalapril (10 mg/kg) twice a day for 5 weeks. After 1 week of active drug therapy, the common carotid and femoral arteries were unilaterally injured by balloon catheterization. In the common carotid arteries, both ACE and chymase activities were increased by the injury, with the increase in chymase activities being greater than that in ACE activities. In the femoral arteries, ACE, but not chymase, activities were significantly increased by the injury. Both candesartan cilexetil and enalapril reduced blood pressure almost equally. Enalapril increased plasma renin activity more strongly than did candesartan cilexetil, and significantly decreased vascular and plasma ACE activities. Candesartan cilexetil significantly suppressed the formation of intima hyperplasia in both the carotid and femoral arteries, while enalapril significantly suppressed intima hyperplasia in the femoral, but not in the carotid arteries. These results indicate that local Ang II production by ACE and chymase is involved in the hyperplasia seen in injured intima, and the difference in the inhibitory action of candesartan and enalapril reflects the extent of contribution of each enzyme. The effect of the ACE inhibitor, enalapril, depended on the activity of ACE, whereas that of the Ang II receptor antagonist, candesartan, was independent of ACE activity.
在犬类实验模型中，研究了由两种不同酶（血管紧张素转换酶（ACE）和糜酶）产生的血管紧张素（Ang）II的作用。该模型通过对颈总动脉和股动脉进行球囊导管插入术诱导内膜增生。动物每天口服坎地沙坦酯（3mg/kg）或依那普利（10mg/kg），持续5周。在积极药物治疗1周后，通过球囊导管插入术对颈总动脉和股动脉进行单侧损伤。在颈总动脉中，损伤后ACE和糜酶活性均增加，糜酶活性的增加大于ACE活性的增加。在股动脉中，损伤后ACE活性显著增加，但糜酶活性未增加。坎地沙坦酯和依那普利降低血压的效果几乎相同。依那普利比坎地沙坦酯更强烈地增加血浆肾素活性，并显著降低血管和血浆ACE活性。坎地沙坦酯显著抑制颈总动脉和股动脉内膜增生的形成，而依那普利显著抑制股动脉内膜增生，但对颈总动脉无此作用。这些结果表明，ACE和糜酶产生的局部Ang II参与了损伤内膜的增生，坎地沙坦和依那普利抑制作用的差异反映了每种酶的作用程度。ACE抑制剂依那普利的作用取决于ACE的活性，而Ang II受体拮抗剂坎地沙坦的作用与ACE活性无关。
