Lakó-Futó Zoltán, Szokodi István, Sármán Balázs, Földes Gábor, Tokola Heikki, Ilves Mika, Leskinen Hanna, Vuolteenaho Olli, Skoumal Réka, deChâtel Rudolf, Ruskoaho Heikki, Tóth Miklós
First Department of Medicine, Semmelweis University, and Molecular Genetic Research Group of the Hungarian Academy of Sciences, Budapest, Hungary.
Circulation. 2003 Nov 11;108(19):2414-22. doi: 10.1161/01.CIR.0000093193.63314.D9. Epub 2003 Oct 20.
The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in cardiac pressure overload.
Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours. Ang II-induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal alpha-actin and beta-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II-induced hypertension. In parallel, Ang II-stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression of vascular endothelial growth factor and fibroblast growth factor-1 was downregulated by Ang II only in the presence of AT2-R blockade.
Our results provide evidence that AT2-R plays a functional role in the cardiac hypertrophic process in vivo by selectively regulating the expression of growth-promoting and growth-inhibiting factors.
血管紧张素II 2型受体（AT2-R）在哺乳动物心脏中的精确功能尚不清楚。在此，我们研究了AT2-R在心脏压力超负荷中的作用。
通过皮下植入渗透微型泵，给大鼠输注溶剂、血管紧张素II（Ang II）、PD123319（一种AT2-R拮抗剂）或Ang II与PD123319的组合，持续12或72小时。PD123319并未改变Ang II诱导的平均动脉压升高、左心室重量/体重比增加以及骨骼肌α-肌动蛋白和β-肌球蛋白重链mRNA水平的升高。相反，在Ang II诱导的高血压中，AT2-R阻断导致c-fos、内皮素-1和胰岛素样生长因子-1的基因表达显著增加。同时，AT2-R阻断显著增强了Ang II刺激的心房利钠肽的mRNA和蛋白质表达。此外，PD123319显著增加了B型利钠肽的合成。此外，仅在存在AT2-R阻断的情况下，Ang II下调了血管内皮生长因子和成纤维细胞生长因子-1的表达。
我们的结果提供了证据，表明AT2-R通过选择性调节促生长和抑生长因子的表达，在体内心脏肥厚过程中发挥功能作用。
