Kim H S, Maeda N, Oh G T, Fernandez L G, Gomez R A, Smithies O
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA.
J Biol Chem. 1999 May 14;274(20):14210-7. doi: 10.1074/jbc.274.20.14210.
Here we investigate the biochemical, molecular, and cellular changes directed toward blood pressure homeostasis that occur in the endocrine branch of the renin-angiotensin system of mice having one angiotensinogen gene inactivated. No compensatory up-regulation of the remaining normal allele occurs in the liver, the main tissue of angiotensinogen synthesis. No significant changes occur in expression of the genes coding for the angiotensin converting enzyme or the major pressor-mediating receptor for angiotensin, but plasma renin concentration in the mice having only one copy of the angiotensinogen gene is greater than twice wild-type. This increase is mediated primarily by a modest increase in the proportion of renal glomeruli producing renin in their juxtaglomerular apparatus and by four times wild-type numbers of renin-producing cells along afferent arterioles of the glomeruli rather than by up-regulating renin production in cells already committed to its synthesis.
在此，我们研究了在一个血管紧张素原基因失活的小鼠肾素-血管紧张素系统的内分泌分支中，针对血压稳态所发生的生化、分子和细胞变化。在血管紧张素原合成的主要组织肝脏中，未发生对其余正常等位基因的代偿性上调。编码血管紧张素转换酶或血管紧张素主要升压介导受体的基因表达未发生显著变化，但仅拥有一份血管紧张素原基因拷贝的小鼠血浆肾素浓度高于野生型的两倍以上。这种增加主要是由在其近球小体中产生肾素的肾小球比例适度增加以及沿肾小球入球小动脉的产肾素细胞数量为野生型的四倍介导的，而不是通过上调已致力于肾素合成的细胞中的肾素产生来实现的。
