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Effect of Ang II on plasma levels of aldosterone. Aldosterone levels in plasma from vehicle-and Ang II–infused animals were determined by radioimmunoassay as described in Methods. Shown is the mean ± SE of duplicate determinations from five rats per condition. The plasma aldosterone levels were significantly increased in Ang II-infused rats relative to controls as indicated by *P<0.01.
Source publication
Angiotensin II (Ang II) is a major regulator of aldosterone secretion in the adrenal zona glomerulosa because it up-regulates the expression of a large number of genes involved in aldosterone biosynthesis. The transport of acetate across adrenocortical cells is a crucial step in the de novo synthesis of cholesterol, the steroid precursor of aldoste...
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Aldosterone-producing zona glomerulosa (zG) cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity. Whether this cyto-architecture also plays functional roles in signaling remains unexplored. To determine if structure informs function, we generated m...
Citations
... In this study, we present the following findings: (1) AngII induces significant upregulation of Ch25h in primary rat VSMCs, (2) Ch25h upregulation is mediated by AT1R through G q/11 signaling and not via a β-arrestin-mediated mechanism, (3) p38 MAPK has a substantial role in Ch25h upregulation, (4) CH25H localizes to the ER in rat VSMCs, and (5) AngII stimulus promotes 25-HC production in primary rat VSMCs. Prior works show that AngII causes gene expression changes in various cell types [44][45][46][47]. Gene expression patterns shape cellular functions and are influenced by external stimuli [48]. ...
Angiotensin II (AngII) is a vasoactive peptide hormone, which, under pathological conditions, contributes to the development of cardiovascular diseases. Oxysterols, including 25-hydroxycholesterol (25-HC), the product of cholesterol-25-hydroxylase (CH25H), also have detrimental effects on vascular health by affecting vascular smooth muscle cells (VSMCs). We investigated AngII-induced gene expression changes in VSMCs to explore whether AngII stimulus and 25-HC production have a connection in the vasculature. RNA-sequencing revealed that Ch25h is significantly upregulated in response to AngII stimulus. The Ch25h mRNA levels were elevated robustly (~50-fold) 1 h after AngII (100 nM) stimulation compared to baseline levels. Using inhibitors, we specified that the AngII-induced Ch25h upregulation is type 1 angiotensin II receptor- and Gq/11 activity-dependent. Furthermore, p38 MAPK has a crucial role in the upregulation of Ch25h. We performed LC-MS/MS to identify 25-HC in the supernatant of AngII-stimulated VSMCs. In the supernatants, 25-HC concentration peaked 4 h after AngII stimulation. Our findings provide insight into the pathways mediating AngII-induced Ch25h upregulation. Our study elucidates a connection between AngII stimulus and 25-HC production in primary rat VSMCs. These results potentially lead to the identification and understanding of new mechanisms in the pathogenesis of vascular impairments.
