The plasma and tissue kininogen-kallikrein-kinin system: Role in the cardiovascular system
The plasma and tissue kininogen-kallikrein-kinin system: Role in the cardiovascular system
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DOI：
10.2174/1568016052773351
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发表时间：
2005-01-05
期刊：
影响因子：
--
通讯作者：
Antunes, E.
中科院分区：
文献类型：
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作者：
Marcondes, S.;Antunes, E.
缓激肽和赖氨酸-缓激肽是涉及哺乳动物的几种生理病理学效应的有效肽介质。它们通过激活G蛋白偶联的组成型B-2或诱导型激肽B-1受体发挥作用，这些受体与涉及增加细胞内Ca++浓度和/或释放包括花生四烯酸代谢物、NO和EDHF在内的介体的信号传导途径有关。在心血管系统中，激肽释放酶-激肽系统对血管平滑肌张力和动脉血压进行精细控制，发挥显著的心脏保护作用。这一点最近在使用过表达人组织激肽释放酶的转基因小鼠和敲除激肽B-1和B-2受体基因的动物的实验研究中得到证实。该系统的紊乱与动脉高血压、心肌缺血和其他临床并发症有关。血管紧张素转化酶（kininase II，ACE）抑制剂已成功应用于心血管疾病患者，但在病理条件下，增强激肽原-激肽释放酶-激肽系统活性的药物或药理学策略仍有很大的研究兴趣。递送含有人组织激肽释放酶基因的腺病毒载体（基因激肽释放酶疗法）已经成为满足这些条件的巨大潜力。本文综述了血浆和组织激肽释放酶-激肽系统的药理学特性、激肽受体和干扰其作用的药物。激肽释放酶-激肽系统对心血管系统的调节作用，特别是对平滑肌张力的调节。和动脉血压以及预防心肌缺血的作用。
Bradykinin and Lys-bradykinin are potent peptide mediators implicated in several physiopathological effects in mammals. They act through activation of G-protein-coupled constitutive B-2 or inducible kinin B-1 receptors linked to signaling pathways involving increased intracellular Ca++ concentrations and/or release of mediaters including arachidonic acid metabolites, NO and EDHF. In the cardiovascular system, the kallikrein-kinin system exerts a fine control of vascular smooth muscle tone and arterial blood pressure, and plays a significant cardioprotective effect. This has been lately confirmed in experimental studies employing transgenic mice overexpressing human tissue kallikrein and animals with knockout of kinin B-1 and B-2 receptor gene. Disturbances in this system are associated with arterial hypertension, myocardial ischaemia and other clinical complications. Inhibitors of kininase II (angiotensin-converting enzyme) have been prescribed successfully to patients with cardiovascular diseases, but there is still a great interest in developing drugs or pharmaco logical strategies that augment the activity of kininogen-kallikrein-kinin system in pathological conditions. Delivery of adenovirus vector containing the human tissue kallikrein gene (gene kallikrein therapy) has emerged as a great potential to satisfy these conditions. This review provides a summary of plasma and tissue kallikrein-kinin system, focusing on the pharmacological properties, kinin receptors and drugs reported to interfere with their actions. The modulatory effects of the kallikrein-kinin system on cardiovascular system, particularly in regulating smooth muscle tone. and arterial blood pressure and in preventing myocardium ischaemia have also been explored in the review.