Zhang Xiaoli, Lassila Markus, Cooper Mark E, Cao Zemin
The JDRF Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia.
Hypertension. 2004 Feb;43(2):276-81. doi: 10.1161/01.HYP.0000113628.94574.0f. Epub 2004 Jan 12.
Angiotensin II is a known stimulus for the expression of vascular endothelial growth factor (VEGF). This action of angiotensin II is mediated by the angiotensin type 1 (AT1) receptor. However, the role of the angiotensin type 2 (AT2) receptor subtype in inducing VEGF expression has been controversial. The aim of the present study was to assess the effects of AT2 receptor blockade on VEGF expression in the retina, initially in experimental diabetic rats induced by injection of streptozotocin. The AT1 receptor antagonist, valsartan, or the AT2 receptor antagonists, PD123319, were administered to diabetic rats for 4 weeks. Increased gene and protein expressions of VEGF, as assessed by real-time reverse transcription-polymerase chain reaction and immunostaining, respectively, were observed in the retina in diabetic rats. Treatment with either valsartan or PD123319 attenuated retinal VEGF expression. To further explore the link between angiotensin receptor subtypes and VEGF expression, valsartan, or PD123319 were administered to rats that were infused with angiotensin II for 2 weeks. VEGF expression was also increased in the retina from angiotensin II infused rats, and this was attenuated by valsartan and PD123319. These findings suggest that VEGF expression is modulated by AT1 and AT2 receptors, thereby implicating angiotensin II receptor subtypes in retinal diseases such as diabetic retinopathy.
血管紧张素II是血管内皮生长因子（VEGF）表达的已知刺激因素。血管紧张素II的这一作用由1型血管紧张素（AT1）受体介导。然而，2型血管紧张素（AT2）受体亚型在诱导VEGF表达中的作用一直存在争议。本研究的目的是评估AT2受体阻断对视网膜中VEGF表达的影响，最初是在通过注射链脲佐菌素诱导的实验性糖尿病大鼠中进行。将AT1受体拮抗剂缬沙坦或AT2受体拮抗剂PD123319给予糖尿病大鼠4周。通过实时逆转录聚合酶链反应和免疫染色分别评估，在糖尿病大鼠的视网膜中观察到VEGF的基因和蛋白表达增加。用缬沙坦或PD123319治疗可减弱视网膜VEGF表达。为了进一步探索血管紧张素受体亚型与VEGF表达之间的联系，将缬沙坦或PD123319给予输注血管紧张素II 2周的大鼠。在输注血管紧张素II的大鼠的视网膜中VEGF表达也增加，而这被缬沙坦和PD123319减弱。这些发现表明VEGF表达受AT1和AT2受体调节，从而提示血管紧张素II受体亚型与糖尿病视网膜病变等视网膜疾病有关。
