Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition

Gómez, R. Ariel; Lynch, Kevin R.; Chevalier, Robert L.; Everett, Allen D.; Johns, D W; Wilfong, N; Peach, Michael J.; Carey, Robert M.

doi:10.1152/ajprenal.1988.254.6.f900

Cited by 119 publications

(86 citation statements)

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“…In adult mammals, low Na ϩ or RAS inhibition by angiotensin-converting enzyme (ACE) inhibitors, such as captopril, upregulate ren mRNA and renin protein (21,80). In combination, low salinity and captopril result in juxtaglomerular cell hypertrophy and renin cell recruitment along renal arterioles (7,18,36,67). Blockade of the RAS cascade arrests the ANG II-mediated negative feedback loop regulating ren transcription and renin cell recruitment (36).…”

Section: Larval Fish Renin Characterizationmentioning

confidence: 99%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

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Section: Larval Fish Renin Characterizationmentioning

confidence: 99%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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“…Renin is traditionally thought to be expressed in the juxtaglomerular apparatus (JGA) and secreted into blood vessels for its endocrine, exocrine, and paracrine functions. However, it has been shown that ACE inhibition increases the staining of renin by recruiting more cells farther along the afferent arterioles by the JGA (82). Further, recent data also identified renin expression along other parts of the nephron, such as the proximal tubules and collecting ducts (165).…”

Section: Nistala Et Al 2066mentioning

confidence: 99%

Redox Control of Renal Function and Hypertension

Nistala

Whaley‐Connell

Sowers

2008

Antioxidants & Redox Signaling

138

123

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“…We have shown that renin precursor cells originate from the metanephric mesenchyme and give rise to JG cells, arteriolar smooth muscle cells (SMCs), mesangial cells, and a subset of proximal tubular cells (30,31). In adult animals, when homeostasis is threatened (such as by dehydration or hypotension) there is an increase in the number of renin-expressing cells along the renal arterioles and in the glomeruli and interstitium, resembling the fetal pattern, a phenomenon called recruitment (5,7). The process does not involve cell replication and/or migration (2), but it occurs by retransformation of arteriolar SMCs and mesangial cells into renin-expressing cells (30).…”

mentioning

confidence: 99%

Transcriptional regulator RBP-J regulates the number and plasticity of renin cells

Rivera

Monteagudo²,

Pentz³

et al. 2011

Physiological Genomics

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scriptional regulator RBP-J regulates the number and plasticity of renin cells. Physiol Genomics 43: 1021-1028, 2011. First published July 12, 2011 doi:10.1152 doi:10. /physiolgenomics.00061.2011 cells are crucial in the control of blood pressure and fluidelectrolyte homeostasis. Notch receptors convey cell-cell signals that may regulate the renin cell phenotype. Because the common downstream effector for all Notch receptors is the transcription factor RBP-J, we used a conditional knockout approach to delete RBP-J in cells of the renin lineage. The resultant RBP-J conditional knockout (cKO) mice displayed a severe reduction in the number of reninpositive juxtaglomerular apparatuses (JGA) and a reduction in the total number of renin positive cells per JGA and along the afferent arterioles. This reduction in renin protein was accompanied by a decrease in renin mRNA expression, decreased circulating renin, and low blood pressure. To investigate whether deletion of RBP-J altered the ability of mice to increase the number of renin cells normally elicited by a physiological threat, we treated RBP-J cKO mice with captopril and sodium depletion for 10 days. The resultant treated RBP-J cKO mice had a 65% reduction in renin mRNA levels (compared with treated controls) and were unable to increase circulating renin. Although these mice attempted to increase the number of renin cells, the cells were unusually thin and had few granules and barely detectable amounts of immunoreactive renin. As a consequence, the cells were incapable of fully adopting the endocrine phenotype of a renin cell. We conclude that RBP-J is required to maintain basal renin expression and the ability of smooth muscle cells along the kidney vasculature to regain the renin phenotype, a fundamental mechanism to preserve homeostasis. juxtaglomerular cells; cell identity; homeostasis; recruitment; conditional knockout; recombination signal binding protein for immunoglobulin kappa J region

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Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition

Cited by 119 publications

References 0 publications

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Redox Control of Renal Function and Hypertension

Transcriptional regulator RBP-J regulates the number and plasticity of renin cells

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