Bastien N R, Ciuffo G M, Saavedra J M, Lambert C
Department of Pharmacology, Université de Montréal, Québec, Canada.
Regul Pept. 1996 May 7;63(1):9-16. doi: 10.1016/0167-0115(96)00012-2.
Paralleling the classic circulating system, recent evidence has demonstrated the presence of a cardiac renin-angiotensin system, as well as the synthesis of angiotensin II in the heart. Two receptors for angiotensin II have been identified and classified as AT1 and AT2. The proportions of these receptor subtypes vary with the tissues, species and stage of development. From the results of other studies, it might be generalized that the expression of angiotensin II receptors and the proportion of AT2 receptor subtype are much higher in fetal and neonatal tissues than in the same tissues from an adult. The aim of this study was to specifically evaluate the AT1/AT2 ratio in the neonatal and adult conduction systems of rat hearts by means of quantitative autoradiogrphy. In the neonatal hearts, angiotensin II binding sites were highly concentrated in the vasculature, arterial duct, and conduction system, whereas their concentrations were barely detectable in the myocardium. Incubation with selective angiotensin II receptor ligands (losartan and CGP 42112) revealed that AT2 was the major subtype in vasculature (86 +/- 3%) and conduction system (73 +/- 4%). In the adult conduction system, the total expression of angiotensin II receptors was greatly reduced meanwhile the AT1 receptors represented the major proportion of the binding sites (80 +/- 3%). Our results demonstrated that the pattern of angiotensin II receptor expression in the conduction system of the rat heart is developmentally regulated. We suggest, as others have already, that the renin-angiotensin system plays a role during the early stage of cardiac development.
与经典的循环系统类似,最近的证据表明心脏中存在肾素 - 血管紧张素系统,以及心脏中血管紧张素II的合成。已鉴定出血管紧张素II的两种受体,并将其分类为AT1和AT2。这些受体亚型的比例随组织、物种和发育阶段而变化。从其他研究结果来看,可以概括地说,胎儿和新生儿组织中血管紧张素II受体的表达以及AT2受体亚型的比例比成人相同组织中的要高得多。本研究的目的是通过定量放射自显影法具体评估大鼠心脏新生儿和成人传导系统中的AT1/AT2比值。在新生儿心脏中,血管紧张素II结合位点高度集中在脉管系统、动脉导管和传导系统中,而在心肌中几乎检测不到它们的浓度。用选择性血管紧张素II受体配体(氯沙坦和CGP 42112)孵育显示,AT2是脉管系统(86±3%)和传导系统(73±4%)中的主要亚型。在成体传导系统中,血管紧张素II受体的总表达大大降低,同时AT1受体占结合位点的主要比例(80±3%)。我们的结果表明,大鼠心脏传导系统中血管紧张素II受体的表达模式受发育调控。我们和其他人一样认为,肾素 - 血管紧张素系统在心脏发育的早期阶段发挥作用。