Correa F M, Viswanathan M, Ciuffo G M, Tsutsumi K, Saavedra J M
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892, USA.
Peptides. 1995;16(1):19-24. doi: 10.1016/0196-9781(94)00150-5.
The aim of the present study was to correlate the development of the renin angiotensin system (RAS) in the kidney of the rat with the development of genetic hypertension. Immature (1-week-old) and adult (12-week-old) normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive kidney rats (SHR) were used for quantification of angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) binding sites using quantitative autoradiography. In both neonatal and adult animals of either strain, ANG II receptors were of AT1 subtype. In all kidney areas of 1-week-old rats. ANG II receptor density was higher in SHR than WKY. Binding density increased with age in WKY rats; thus, in the glomeruli and the outer stripe of the outer medulla of 12-week-old WKY, binding was significantly higher than that present in age-matched SHR. [125I]351A binding to ACE was highest in the outer medulla and not detectable in glomeruli. In 1-week-old rats, binding to ACE was higher in WKY than in SHR strain. No differences in ACE binding were found between adult SHR and WKY rats, with the exception of the inner stripe of the outer medulla, where no binding was detected in SHR. Our results support the hypothesis that the RAS in kidney is developmentally regulated and is involved in the development and maintenance of genetic hypertension in SHR.
本研究的目的是将大鼠肾脏中肾素血管紧张素系统（RAS）的发育与遗传性高血压的发展联系起来。使用未成熟（1周龄）和成年（12周龄）的正常血压Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR），采用定量放射自显影法对血管紧张素II（ANG II）受体和血管紧张素转换酶（ACE）结合位点进行定量分析。在这两个品系的新生和成年动物中，ANG II受体均为AT1亚型。在1周龄大鼠的所有肾脏区域，SHR的ANG II受体密度均高于WKY。WKY大鼠的结合密度随年龄增加；因此，在12周龄WKY大鼠的肾小球和外髓质外带中，结合显著高于年龄匹配的SHR。[125I]351A与ACE的结合在外髓质中最高，在肾小球中未检测到。在1周龄大鼠中，WKY品系与ACE的结合高于SHR品系。成年SHR和WKY大鼠之间的ACE结合没有差异，但外髓质内带除外，在SHR中未检测到结合。我们的结果支持以下假设，即肾脏中的RAS在发育过程中受到调节，并参与SHR遗传性高血压的发生和维持。
