Clozel J P, Müller R K, Roux S, Fischli W, Baumgartner H R
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Circulation. 1993 Sep;88(3):1222-7. doi: 10.1161/01.cir.88.3.1222.
Angiotensin converting enzyme (ACE) inhibition has been shown to prevent neointima formation after vascular injury in rats. However, clinical results evaluating restenosis after angioplasty have been negative. The goal of the present study was to evaluate the influence of the renin-angiotensin system (RAS) status on the effect of ACE inhibition on neointima formation.
Arterial injury was produced by ballooning the left carotid artery of rats, and neointima formation was evaluated by morphometry 2 weeks after ballooning. The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA). In parallel groups of rats, measurement of plasma renin activity was made in order to characterize (at least at the plasma level) the status of the RAS. As expected, renal artery stenosis markedly increased plasma renin activity, and DOCA decreased it to undetectable levels. Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats.
We conclude that the status of the RAS has a major influence on the effect of cilazapril on neointima formation after vascular injury.
血管紧张素转换酶（ACE）抑制已被证明可预防大鼠血管损伤后新生内膜的形成。然而，评估血管成形术后再狭窄的临床结果却是阴性的。本研究的目的是评估肾素 - 血管紧张素系统（RAS）状态对ACE抑制新生内膜形成效果的影响。
通过对大鼠左颈动脉进行球囊扩张造成动脉损伤，并在球囊扩张后2周通过形态学测量评估新生内膜形成情况。在四个实验组中评估西拉普利的效果：正常血压大鼠、自发性高血压大鼠、通过夹闭诱导肾动脉狭窄的高血压大鼠（双肾单夹大鼠）以及进行单侧肾切除、高盐饮食并给予脱氧皮质酮（DOCA）的高血压大鼠。在平行的大鼠组中，测量血浆肾素活性以（至少在血浆水平）表征RAS的状态。正如预期的那样，肾动脉狭窄显著增加血浆肾素活性，而DOCA将其降低至检测不到的水平。西拉普利对正常血压大鼠、自发性高血压大鼠和双肾单夹大鼠的新生内膜形成具有显著的预防作用，但对DOCA大鼠无效。
我们得出结论，RAS的状态对西拉普利对血管损伤后新生内膜形成的效果有重大影响。
