Disease relevance of Agt

• The importance of K for the hyperaldosteronism during dietary Na restriction was verified by the observation that superimposition of K restriction led to hypotension in Agt+/+ and uniform death in Agt-/- mice along with a reduction in P(aldo) by 75 and 90%, respectively [1].
• This genetic manipulation overcame the hypotension of AOGEN-deficient mice and even caused hypertension indistinguishable in its extent from the parent transgenic mice with an intact endogenous AOGEN gene [2].

High impact information on Agt

• In all Agt genotypes, UUO reduced ipsilateral renal mass and increased that of the opposite kidney [3].
• These abnormal phenotypes are quantitatively similar to those found in mutant mice homozygous for the angiotensinogen gene (Agt-/-), indicating that major biological functions of endogenous Ang elucidated by the abnormal phenotypes of Agt-/- are mediated by the AT1 receptors [4].
• Plasma aldosterone levels (P(aldo)) were comparable during NS, and similarly elevated during LS in Agt+/+ and Agt-/-. Moreover, in both, the elevation in P(aldo) was accompanied by marked increase in adrenal zona glomerulosa cells and adrenal P450aldo mRNA [1].
• The marked gender differences in gene expression in wild-type mice and the changes induced by moderate alterations in Agt expression and BP emphasize the need to look for similar differences in humans [5].
• A highly significant correlation between renal expression of the angiotensin type 1a receptor and kallikrein, independent of Agt genotype, is present in females (P < 0.0001) but not males (P = 0.4) [5].

Biological context of Agt

• This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt-/-) and angiotensin-converting enzyme-deficient (Ace -/-) mice that are unable to synthesize angiotensin II [6].
• The downregulation of Aogen in myocytes from FVB.Igf+/- mice was characterized by a reduction in Ang II [7].
• Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation [8].
• These "gene titration" experiments establish that changes in Agt gene expression cause changes in the blood pressures of mice [9].
• The ratio of postcoital plugs to subsequent litters was 4.0 and 1.2 for Agt(-/-) and Agt(+/+) breedings, respectively (P = 0.03) [10].

Anatomical context of Agt

• In the present study, we examined mechanical stretch-induced activation of mitogen-activated protein kinases (MAP kinases) using cultured cardiac myocytes derived from neonatal angiotensinogen gene deficient mice (Agt-/-) and neonatal wild type mice (Agt+/+) [11].
• RESULT(S): The mean number of oocytes harvested was greatest in wild-type mice (two copies of Agt, 39.9 +/- 14) with a reduction of ovulatory capacity in mice overexpressing Agt (three copies [34.8 +/- 11.7] and four copies [31.2 +/- 12.4], P =.026) [12].
• Mice bearing one, two, three, or four copies of the Agt gene underwent renal artery clipping to induce high-renin two-kidney, one-clip renovascular hypertension (2K1C), or uninephrectomy, salt loading, and application of deoxycorticosterone-acetate (DOCA) pellets to induce low-renin mineralocorticoid hypertension [13].

Associations of Agt with chemical compounds

• Ovarian histology, serum estradiol levels, and early embryonic development were independent of the Agt genotype [12].
• CV-11974 failed to suppress the stretch-induced activation of MAP kinases in Agt-/- cardiac myocytes while it inhibited the activation in Agt+/+ cardiac myocytes [11].
• There was a trend towards less suppression of endogenous aldosterone by DOCA treatment with increasing number of Agt gene copies [13].

Regulatory relationships of Agt

• Furthermore, hypertension-induced alterations in kidney histology and function were less pronounced in crossbred mice than in equally hypertensive animals expressing AOGEN locally [2].

Other interactions of Agt

• Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased [7].
• We conclude that Nos3 and Agt are important genes in the regulation of blood pressure during pregnancy [14].
• Linkage of Agt and Actsk-1 to distal mouse chromosome 8 loci: a new conserved linkage [15].
• Analysis of the segregation patterns closely linked Agt to Aprt and Emv-2, which places the angiotensinogen locus on the distal end of mouse Chr 8 [15].
• This intracisternal A-particle, named IAP-Agt, segregated concordantly with angiotensinogen expression phenotypes in CXB recombinant inbred mice [16].

Analytical, diagnostic and therapeutic context of Agt

• We have used gene targeting to vary the amounts of angiotensinogen and angiotensin-converting enzyme (ACE) synthesized from their genes (Agt and Ace) [9].

References