Ratliff Brian, Rodebaugh Justin, Sekulic Miroslav, Solhaug Michael
Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23501-1980, USA.
Pediatr Nephrol. 2007 Aug;22(8):1135-42. doi: 10.1007/s00467-007-0489-z. Epub 2007 Apr 17.
Glomerular maturation increases from immature superficial to advanced juxtamedullary nephrons, while nephrogenesis continues postnatally in porcine kidneys. Endothelial NOS, eNOS, shows significant postnatal renal developmental regulation, perhaps mediated by Angiotensin II (AII). The objective was to compare eNOS mRNA gene expression between superficial and juxtamedullary glomeruli obtained from piglets and adult pigs utilizing laser capture microdissection during basal conditions and, to determine the role of the AII AT1 receptor, AT1, after chronic AT1 inhibition (AT1X) with candesartan. Superficial glomerular eNOS expression was lowest in newborns (NB) and at 7 days, and was highest in 14, 21 day old piglets and adults. Juxtamedullary glomerular eNOS, while similar in NB, 14, 21 day and adult, dipped to the lowest level at 7 days. Juxtamedullary glomerular eNOS expression in the NB was 7 fold greater than in superficial glomeruli. AT1X did not change eNOS expression in adult glomeruli. AT1X significantly reduced NB eNOS expression in both superficial, 90+/-10%, and juxtamedullary glomeruli, 89+/-5% respectively. In conclusion, eNOS gene expression demonstrates significant differences between NB superficial and juxtamedullary glomeruli, significant postnatal developmental regulation of both glomerular locations, and this expression may be mediated in the NB by AII via the AT1 receptor.
从不成熟的浅表肾单位到成熟的近髓肾单位,肾小球成熟度逐渐增加,而猪肾脏在出生后肾发生仍在继续。内皮型一氧化氮合酶(eNOS)在出生后肾脏发育过程中受到显著调控,可能由血管紧张素II(AII)介导。本研究旨在比较基础状态下利用激光捕获显微切割技术从仔猪和成年猪获取的浅表肾小球和近髓肾小球之间eNOS mRNA基因表达情况,并确定在使用坎地沙坦进行慢性AT1受体抑制(AT1X)后AII AT1受体(AT1)的作用。浅表肾小球eNOS表达在新生儿(NB)和7日龄时最低,在14、21日龄仔猪及成年猪中最高。近髓肾小球eNOS表达在NB、14、21日龄及成年猪中相似,但在7日龄时降至最低水平。NB近髓肾小球eNOS表达比浅表肾小球高7倍。AT1X对成年肾小球eNOS表达无影响。AT1X分别使NB浅表肾小球和近髓肾小球的eNOS表达显著降低,降幅分别为90±10%和89±5%。总之,eNOS基因表达在NB浅表和近髓肾小球之间存在显著差异,在两个肾小球位置均有显著的出生后发育调控,且在NB中这种表达可能由AII通过AT1受体介导。