Gomez R A, Lynch K R, Chevalier R L, Wilfong N, Everett A, Carey R M, Peach M J
Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville 22908.
Am J Physiol. 1988 Apr;254(4 Pt 2):F582-7. doi: 10.1152/ajprenal.1988.254.4.F582.
To determine whether angiotensinogen (Ao) and renin are synthesized by the immature kidney and to assess the changes in intrarenal renin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and Ao relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and Ao cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I.h-1.mg protein-1 in the incubation media. RRC was higher in newborn than in adult SHR (979 +/- 164 vs. 206 +/- 47) and WKY (573 +/- 69 vs. 297 +/- 74) (P less than 0.05). In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animal. Ao mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and Ao genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.
为了确定血管紧张素原(Ao)和肾素是否由未成熟肾脏合成,并评估成熟过程中肾内肾素分布的变化,我们使用高度特异性的抗大鼠肾素抗体,对24只新生以及12只成年Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)的肾脏进行肾素免疫细胞化学处理。采用Northern和斑点印迹技术,使用全长大鼠肾素和Ao cDNA,检测肾脏肾素和Ao相对mRNA水平(mRNA/总RNA)。通过对血管紧张素I(ANG I)进行放射免疫测定来测量肾素浓度(RRC),并以孵育介质中每毫克蛋白质每小时的纳克数(ng ANG I·h-1·mg蛋白质-1)表示。新生SHR的RRC高于成年SHR(979±164 vs. 206±47),新生WKY的RRC高于成年WKY(573±69 vs. 297±74)(P<0.05)。在两种大鼠品系的新生肾脏中,肾素分布于入球小动脉和小叶间动脉的全长,而在成年肾脏中,肾素局限于经典的球旁位置。随着成熟,含有肾素的免疫反应性球旁器和动脉段的比例下降。新生动物肾脏的肾素mRNA水平比成年动物高7.9倍。在两种大鼠品系的新生和成年肾脏中均检测到Ao mRNA。本研究确凿地证明,肾素和Ao基因在新生肾脏中均有表达,为局部肾素-血管紧张素系统存在发育变化提供了证据。