Chymase-dependent angiotensin II formation in human blood vessels
Chymase-dependent angiotensin II formation in human blood vessels
复制标题
DOI：
10.1038/sj.jhh.1001022
复制
发表时间：
2000-06-01
影响因子：
2.7
通讯作者：
Borland, JAA
中科院分区：
文献类型：
--
作者：
Chester, AH;Borland, JAA
肾素-血管紧张素途径的药理调节已被证明在许多心血管疾病中是有益的。1-4这一治疗策略的主要目的是通过抑制血管紧张素转换酶(ACE)来阻断效应肽--血管紧张素II的形成。然而，血管紧张素II水平已被证明在接受慢性血管紧张素转换酶抑制剂治疗后恢复到治疗前的水平，并且通过血管紧张素受体拮抗剂和血管紧张素转换酶抑制剂联合应用，血压的降低可以达到比单独使用血管紧张素转换酶抑制剂更大的降压效果。此外，运动后或缺血期间血浆血管紧张素II的增加不能被血管紧张素转换酶抑制剂阻止。7、8血管紧张素II形成的替代途径的概念得到了体内和体外实验的支持。例如，仅有ACE抑制剂已被证明不能完全阻断人类心脏和逼尿肌中血管紧张素II的生成，或阻断血管紧张素I在分离血管中的收缩作用。9-12这些观察表明，存在替代的血管紧张素II形成途径，这可能限制ACE抑制剂治疗的临床疗效。
Pharmacological modulation of the renin-angiotensin pathway has been shown to be of benefit in a number of cardiovascular diseases. 1–4 The mainstay of this therapeutic strategy is to block the formation of effector peptide, angiotensin II, by inhibition of angiotensin-converting enzyme (ACE). However, angiotensin II levels have been shown to return to pre-treatment levels following chronic ACE inhibitor therapy, and reductions in blood pressure greater than those observed with ACE inhibitors alone can be obtained by co-administration of angiotensin receptor antagonists with an ACE inhibitor. 5, 6 In addition, increases in plasma angiotensin II following exercise or during ischaemic conditions could not be prevented by an ACE inhibitor. 7, 8 The concept of alternative pathways for angiotensin II formation is supported by a number of in vivo and in vitro experiments. For example, ACE inhibitors alone have been shown to be unable to completely block angiotensin II generation in the human heart and detrusor muscle or block the contractile effect of angiotensin I in isolated blood vessels. 9–12 These observations suggest the existence of alternative angiotensin II formation pathways which may limit the clinical efficacy of ACE inhibitor therapy.