Song K, Kurobe Y, Kanehara H, Okunishi H, Wada T, Inada Y, Nishikawa K, Miyazaki M
Department of Pharmacology, Osaka Medical College, Japan.
Blood Press Suppl. 1994;5:21-6.
Angiotensin II (Ang II) receptors were labelled by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand in the kidney, adrenal gland, thoracic aorta, and hindbrain of adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ang II receptors were differentiated into subtypes by susceptibility to subtype 1 (AT1) and subtype 2 (AT2) antagonists. In both rat strains, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors in glomeruli, proximal tubules, and the outer medulla. AT1 receptors were predominant in the thoracic aorta. The nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DM10), area postrema, and spinal trigeminal nucleus (Sp5) contained exclusively AT1 receptors, whereas the nucleus of the inferior olive contained AT2 receptors predominantly. Significant differences in receptor density were observed between SHR and WKY. The adrenal cortex, renal outer medulla, NTS, DM10, and Sp5 displayed higher AT1 receptor density in SHR than in WKY. These results indicate that expression of AT1 receptors is regulated differently in important targets of Ang II in SHR, and suggest that altered regulation of AT1 receptor expression may be relevant to the pathogenesis of hypertension in SHR.
采用体外放射自显影法,以125I-[Sar1,Ile8]血管紧张素II(Ang II)为配体,对成年自发性高血压大鼠(SHR)和正常血压的Wistar-Kyoto大鼠(WKY)的肾脏、肾上腺、胸主动脉和后脑的Ang II受体进行标记。通过对1型(AT1)和2型(AT2)拮抗剂的敏感性将Ang II受体分为不同亚型。在两种大鼠品系中,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。肾脏的肾小球、近端小管和外髓质仅含有AT1受体。胸主动脉中AT1受体占主导。孤束核(NTS)、迷走神经背运动核(DM10)、最后区和三叉神经脊束核(Sp5)仅含有AT1受体,而下橄榄核主要含有AT2受体。在SHR和WKY之间观察到受体密度存在显著差异。SHR的肾上腺皮质、肾外髓质、NTS、DM10和Sp5的AT1受体密度高于WKY。这些结果表明,SHR中Ang II重要靶器官中AT1受体的表达受到不同调节,提示AT1受体表达调节的改变可能与SHR高血压的发病机制有关。