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通过体外放射自显影法对自发性高血压大鼠外周组织中血管紧张素II受体亚型进行定位。

Mapping of angiotensin II receptor subtypes in peripheral tissues of spontaneously hypertensive rats by in vitro autoradiography.

作者信息

Song K, Kurobe Y, Kanehara H, Wada T, Inada Y, Nishikawa K, Miyazaki M

机构信息

Department of Pharmacology, Osaka Medical College, Japan.

出版信息

Clin Exp Pharmacol Physiol Suppl. 1995 Dec;22(1):S17-9. doi: 10.1111/j.1440-1681.1995.tb02868.x.

Abstract
  1. The regulation of angiotensin II (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats. 2. AII receptor binding was determined by a quantitative in vitro autoradiography using [125I]-[Sar1,Ile8]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV-11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]-[Sar1,Ile8]AII to differentiate AT1 and AT2 receptor binding. 3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart. 4. As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats. 5. These results indicate that the expression of AT1 receptors is differently regulated in some important targets of AII in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the pathophysiological features of SHR.
摘要
  1. 研究了20周龄雄性自发性高血压大鼠(SHR)和年龄匹配的正常血压Wistar-Kyoto(WKY)大鼠外周组织中血管紧张素II(AII)受体亚型的调节情况。2. 使用[125I]-[Sar1,Ile8]AII作为配体,通过定量体外放射自显影法测定肾脏、肾上腺、胸主动脉和心脏中的AII受体结合情况。使用特异性AT1受体拮抗剂CV-11974和特异性AT2拮抗剂CGP42112B与[125I]-[Sar1,Ile8]AII竞争,以区分AT1和AT2受体结合。3. SHR和WKY大鼠中各亚型的相对丰度非常相似。在两种品系的大鼠中,肾上腺皮质主要含有AT1受体,而肾上腺髓质中AT2受体占主导。肾脏在肾小球、近端小管和外髓质中仅含有AT1受体。AT1受体在胸主动脉和心脏中占主导。4. 至于相对受体密度,在SHR和WKY大鼠之间观察到重要差异。在SHR中,肾上腺皮质、肾脏外髓质和心脏的AT1受体密度高于WKY大鼠。5. 这些结果表明,SHR中AII的一些重要靶标中AT1受体的表达受到不同调节,并表明本研究中呈现的AT1受体调节改变应与SHR的病理生理特征相关。

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