Angiotensin II receptor gene expression in the hypertensive endorgan damages and the effect of the treatment.

血管紧张素II受体基因表达在高血压内脏器损伤及治疗中的作用。

基本信息

批准号：
05670617
负责人：
KOHARA Katsuhiko
金额：
$ 1.47万
依托单位：
Ehime University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

The levels of AT1A and AT1B receptor mRNA expression were evaluated by RT-PCR in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). At the age of 16-week old, there was no difference in AT1 receptor subtypes expression in the heart, adrenal gland or kidney between SHR and WKY except for the aorta in which AT1B was less expressed in SHR.Antihypertensive treatment with either AT1 receptor antagonist or ACE inhibitor resulted in regression of left ventricular hypertrophy in SHR.After one week of the treatment, At1 receptor antagonist significantly decreased both AT1A and AT1B receptor mRNA expression, and ACE inhibitor significantly increased the levels of AT1A mRNA in the left ventricle of SHR.However, after four week of the treatment with both AT1 receptor antagonist and ACE inhibitor, the levels of AT1A and AT1B mRNA were returned to the control levels.Using newly developed method, we evaluated the AT2 gene expression in rat adrenal gland. Bilateral nephrectomy as well as exogenous Ang II administration significantly increased the gene expression of AT2 mRNA in the rat adrenal gland. Althogh the property of AT2 receptor in the adrenal gland is still unknown, these findings indicate that alteration of the renin-angiotensin system can change the AT2 receptor gene expression.Results obtained in the study indicate that Ang II receptor shows subtype specific changes in a tissue specific manner.

通过 RT-PCR 评估自发性高血压大鼠 (SHR) 和 Wistar-Kyoto 大鼠 (WKY) 中 AT1A 和 AT1B 受体 mRNA 表达水平。 16周龄时，除SHR中AT1B表达较少的主动脉外，SHR和WKY之间心脏、肾上腺或肾脏中AT1受体亚型表达没有差异。使用任一AT1受体拮抗剂进行降压治疗或 ACE 抑制剂导致 SHR 左心室肥厚消退。治疗 1 周后，At1 受体拮抗剂显着降低 AT1A 和 AT1B 受体 mRNA 表达，以及 ACE抑制剂显着增加了SHR左心室AT1A mRNA的水平。然而，使用AT1受体拮抗剂和ACE抑制剂治疗4周后，AT1A和AT1B mRNA的水平恢复到对照水平。使用新开发的方法，我们评估了大鼠肾上腺中 AT2 基因的表达。双侧肾切除术以及外源性Ang II给药显着增加了大鼠肾上腺中AT2 mRNA的基因表达。尽管肾上腺中 AT2 受体的特性仍不清楚，但这些发现表明肾素-血管紧张素系统的改变可以改变 AT2 受体基因表达。研究结果表明，Ang II 受体在组织中表现出亚型特异性变化具体方式。