Homeostasis in Mice with Genetically Decreased Angiotensinogen Is Primarily by an Increased Number of Renin-producing Cells

Abstract

Here we investigate the biochemical, molecular, and cellular changes directed toward blood pressure homeostasis that occur in the endocrine branch of the reninangiotensin 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 pressormediating 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 upregulating renin production in cells already committed to its synthesis.

The MicroRNA-Processing Enzyme Dicer Maintains Juxtaglomerular Cells

“…We previously showed a direct relationship between the number of cells that synthesize renin and the levels of renin mRNA and circulating renin. 28 Thus, we hypothesize that the decreased circulating renin and renin gene expression found in this study are attributable to the significant drop in the number of JG cells.…”

Physiology of the Renal Interstitium

“…In this context, there is ample evidence that juxtaglomerular renin-producing cells are progeny of renin-positive precursor cells (cells that also give rise to perivascular fibroblast-like cells, which can be recruited to produce renin when needed). This concept is mainly based on studies that analyzed kidneys of Ren-1d-Cre;R26STOPlacZ and Ren-1d-Cre;Z/EG double transgenic mice as well as in Ren-1d-Cre;R26STOPlacZ ;ATGF2/2 composite mice (in these mice, angiotensinogen deficiency causes additional recruitment of renin-producing cells [96]), which documented common lineage for perivascular fibroblasts and renin-producing juxtaglomerular cells (70,79). These aforementioned renin precursor cells are presumably progeny of FoxD1-positive progenitor cells, but this information has been disclosed only as "unpublished data" (Figure 3) (97).…”

Ren1c Homozygous Null Mice Are Hypotensive and Polyuric, but Heterozygotes Are Indistinguishable from Wild-Type

“…The distribution and the number of renin-producing cells were determined as described previously (7,12,13).…”