血管紧张素Ⅱ受体与高血压性心肌重塑

Angiotensin II receptor and myocardial remodeling in hypertension

血管紧张素Ⅱ（angiotensinⅡ,AngⅡ）是肾素-血管紧张素系统（RAS）的效应因子,通过其受体介导生物学效应。放射配基结合分析证实哺乳动物存在AT_1、AT_2受体,大鼠和小鼠AT_1受体存在AT_(1A)、AT_(1B)、和AT(1C)受体亚型。近年来还发现了AT_3和AT_4受体亚型,但结构和功能不清。AT_1受体具有G蛋白耦联受体超家族的特性,有7个螺旋的跨膜段,与其他G蛋白受体有20％～30％同源性,主要分布于成年动物血管、心、肾上腺等;AT_2受体仅有32％氨基酸序列与AT_1受体同源,主要分布于胚胎组织和间质组织。最新研究显示AngⅡ绝大多数生物学效应都是AT_1受体介导的。AngⅡ刺激AT_1受体诱导c-fos、c-jun和c-myc等原癌基因的表达,引起心肌细胞肥大,成纤维细胞增殖和间质胶原沉积,AT_1受体拮抗剂能逆转高血压所致的心肌肥厚,减少胶原积累,AT_2受体拮抗剂无此作用。AT_2受体的生物学效应知之甚少,可能在抑制生长因子引起的细胞增殖、对抗AT_1受体的促细胞有丝分裂作用和诱导细胞凋亡中起作用。心肌组织AT_1和AT_2受体可能共同调节了高血压心肌重塑的发生发展。

Angiotensin II (Ang II ) is an effector of rein-angiotensin system. Ang II receptors mediate its biological effects. An analysis of radioactive ligand demostrated that mammalian exists AT1 receptor and AT2 receptor subtype. AT1 receptor exists three isoforms, AT1A, AT1B and AT1c receptor subtype in rat and mouse. The AT3 and the AT4 subtype receptors had been cloned, but their structure and function were unknown. The AT1 receptor belongs to the superfamily of seven trans-membrane domain, G-protein-coupled receptors and was 20%~ 30% homologous to other G-protein-coupled receptors. The AT1 receptor mainly exists in vessel, heart and adrenal glands in adult animals. The AT2 receptor only has 32% amino acid sequences homologous to AT1 receptor and mainly exists in embronic tissue and intersti-tium. Recent studies have shown that the AT1 receptor may mediate most of the biological functionof Ang I . The AT1 receptor mediates promoting the expression of growth-related inducible transcription factors such as c-fos, c-jun and c-myc, and inducing myocardial cell hypertrophy, cardiac fibroblasts proliferation and interstitial collagen deposition. The AT1 receptor antagonist can reverse myocardial hypertrophy and collagen accumulation induced by hypertension, but the AT2 receptor antagonist can't. The biological function of the AT2 receptor is little known. The AT2 receptor may mediate inhibit on of growth factor-induced cell proliferation, oposite AT1 receptor-induced mi-togenic effect and induce apoptosis. The AT1 receptor and AT2 receptor subtype in myocardial tissue may regulate the genesis and development of myocardial remodeling in hypertension togather.