Aldosterone enhances renin gene expression in juxtaglomerular cells

2004 ◽  
Vol 286 (2) ◽  
pp. F349-F355 ◽  
Author(s):  
Jürgen Klar ◽  
Helga Vitzthum ◽  
Armin Kurtz
Keyword(s):  
Gene Expression ◽  
Primary Cultures ◽  
Cellular Level ◽  
Juxtaglomerular Cells ◽  
Mrna Levels ◽  
Renin Synthesis ◽  
Corticosteroid Hormones ◽  
Renin Gene ◽  
Renin Mrna ◽  
Mrna Half Life

The secretion and synthesis of renin as the key regulator of the renin-angiotensin-aldosterone system are directly controlled by ANG II in the sense of a negative feedback. Because we found that renal afferent arterioles including the juxtaglomerular portion express the mineralocorticoid receptor, we aimed to characterize a possible direct effect of aldosterone on renin synthesis and renin secretion at the level of renal juxtaglomerular cells. Aldosterone (100 nM) clearly enhanced renin mRNA levels in primary cultures of mouse juxtaglomerular cells prestimulated with isoproterenol (100 nM) but had no effect on the exocytosis of stored renin. Similarly, in the mouse juxtaglomerular cell line As4.1, aldosterone time and concentration dependently increased renin mRNA abundance and prorenin secretion up to 2.5-fold. Moreover, aldosterone potentiated cAMP-induced renin gene expression in As4.1 cells. The effect of aldosterone was inhibited by spironolactone and was mimicked by corticosteroid hormones but not by sex steroids. Aldosterone had no influence on basal renin promoter activity but increased the renin mRNA half-life about threefold. In summary, these data suggest that aldosterone exerts a direct positive effect on renin gene expression at the cellular level probably by stabilizing renin mRNA.

Tumor necrosis factor-α inhibits renin gene expression

2002 ◽  
Vol 283 (5) ◽  
pp. R1046-R1051 ◽  
Author(s):  
Vladimir Todorov ◽  
Markus Müller ◽  
Frank Schweda ◽  
Armin Kurtz
Keyword(s):  
Gene Expression ◽  
Knockout Mice ◽  
Primary Cultures ◽  
Cellular Level ◽  
Renin Synthesis ◽  
Tnf Α ◽  
Renin Gene ◽  
Renin Mrna ◽  
Vascular Proliferation ◽  
Factor Α

Renin, produced in renal juxtaglomerular (JG) cells, is a fundamental regulator of blood pressure. Accumulating evidence suggests that cytokines may directly influence renin production in the JG cells. TNF-α, which is one of the key mediators in immunity and inflammation, is known to participate in the control of vascular proliferation and contraction and hence in the pathogenesis of cardiovascular diseases. Thus TNF-α may exert its effects on the cardiovascular system through modulation of renal renin synthesis. Therefore we have tested the effect of TNF-α on renin transcription in As4.1 cells, which represent transformed mouse JG cells, and in native mouse JG cells in culture. Renin gene expression was also determined in mice lacking the gene for TNF-α (TNF-α knockout mice). TNF-α inhibited renin gene expression via an inhibition of the transcriptional activity, targeting the proximal 4.1 kb of the renin promoter in As4.1 cells. TNF-α also attenuated forskolin-stimulated renin gene expression in primary cultures of mouse JG cells. Mice lacking the TNF-α gene had almost threefold higher basal renal renin mRNA abundance relative to the control strain. The general physiological regulation of renin expression by salt was not disturbed in TNF-α knockout mice. Our data suggest that TNF-α inhibits renin gene transcription at the cellular level and thus may act as a modulator of renin synthesis in (physio)pathological situations.

Acute hypoxia stimulates renin secretion and renin gene expression in vivo but not in vitro

1997 ◽  
Vol 272 (4) ◽  
pp. R1105-R1111 ◽  
Author(s):  
T. Ritthaler ◽  
K. Schricker ◽  
F. Kees ◽  
B. Kramer ◽  
A. Kurtz
Keyword(s):  
Gene Expression ◽  
Acute Hypoxia ◽  
Primary Cultures ◽  
Renin Secretion ◽  
Plasma Norepinephrine ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Renin Gene ◽  
Renin Mrna

This study aimed at examining the influence of acute hypoxia on renin secretion and renin gene expression in the kidney. To this end, male Sprague-Dawley rats were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for 6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined. PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively. Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary cultures of renal juxtaglomerular cells had no influence on renin secretion and renin gene expression after 6 and 20 h. Our findings thus suggest that both arterial and venous hypoxia can be powerful stimulators of renin secretion and renin gene expression in vivo. Because renal denervation did not prevent stimulation of the renin system by hypoxia, the effect could be indirectly mediated via the baroreceptor-macula densa mechanism. Another potential mediator of the effect could be circulating catecholamines, since we found that plasma norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation, respectively.

JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter

1999 ◽  
Vol 277 (4) ◽  
pp. F634-F642 ◽  
Author(s):  
Patrick L. Sinn ◽  
Xiaoji Zhang ◽  
Curt D. Sigmund
Keyword(s):  
Gene Expression ◽  
Systemic Circulation ◽  
Proximal Promoter ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Specific Expression ◽  
Renin Synthesis ◽  
Human Renin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Cell Expression

In the kidney, renin gene expression is exquisitely localized to the juxtaglomerular (JG) cells lining the afferent arteriole, having the capacity to regulate renin synthesis in response to a variety of physiological cues. We investigated human renin gene expression in transgenic mice containing a genomic construct driven by 149 bp of its proximal promoter to elucidate whether this was sufficient to confer JG-specific expression. Whereas human renin mRNA was permissively expressed in most tissues, the transgene was expressed mainly in JG cells in the kidney. Active human renin and human prorenin were found in the systemic circulation at levels consistent with previous transgenic models. Remarkably, two lines displayed an appropriate upregulation of transgene mRNA in response to angiotensin-converting enzyme inhibition, and two lines exhibited a downregulation of transgene mRNA in response to subpressor and pressor doses of ANG II. Our results suggest that 149 bp of the human renin proximal promoter, in a context of a genomic construct, are sufficient to confer human renin expression in renal JG cells and at least some aspects of appropriate regulation.

Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life

1992 ◽  
Vol 262 (3) ◽  
pp. R459-R463 ◽  
Author(s):  
W. V. Page ◽  
S. Perlman ◽  
F. G. Smith ◽  
J. L. Segar ◽  
J. E. Robillard
Keyword(s):  
Gene Expression ◽  
Plasma Renin ◽  
Renal Nerves ◽  
Mrna Levels ◽  
Angiotensin I ◽  
Fetal Sheep ◽  
Close Analysis ◽  
Renin Gene ◽  
Renin Mrna

The role of renal nerves in regulating changes in plasma renin activity (PRA) and renal renin gene expression was studied in intact (n = 6) and denervated (n = 6) fetal sheep before birth and during the first 24 h after delivery. Renal denervation completely blunted the rise in PRA observed 24 h after delivery in newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys, predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than 0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of these results also revealed that renin mRNA levels were significantly higher (P less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3) than in newborn lambs delivered by cesarean section (n = 3). These results suggest that renal nerves play an important role in regulating renin gene expression and PRA during the transition from fetal to newborn life.

Distribution of renin mRNA and its protein in the developing kidney

1989 ◽  
Vol 257 (5) ◽  
pp. F850-F858 ◽  
Author(s):  
R. A. Gomez ◽  
K. R. Lynch ◽  
B. C. Sturgill ◽  
J. P. Elwood ◽  
R. L. Chevalier ◽  
...  
Keyword(s):  
Kidney Tissue ◽  
Juxtaglomerular Apparatus ◽  
Mrna Levels ◽  
Renal Vasculature ◽  
Renin Synthesis ◽  
Adult Kidney ◽  
Renin Gene ◽  
Renin Mrna ◽  
Developing Kidney ◽  
Wistar Kyoto

The intrarenal distribution of renin changes markedly during maturation. To determine whether renin gene expression changes along the developing renal vasculature, renin mRNA distribution was assessed using in situ hybridization histochemistry. Fetal, newborn, and adult kidney tissue sections from Wistar-Kyoto rats were hybridized with an oligonucleotide complementary to rat renin mRNA. In fetal kidneys, renin mRNA was found in the vascular pole of juxtamedullary glomeruli and along afferent, interlobular, and arcuate arteries. In kidneys from newborn rats, renin mRNA localized throughout the whole length of afferent arterioles, but was not detected in interlobular or arcuate arteries. In adult kidneys, hybridization signals were less intense and confined to the juxtaglomerular apparatus. Immunolocalization of renin with a polyclonal anti-rat renin antibody paralleled closely the mRNA distribution. Northern blot analyses demonstrated that renin mRNA levels were higher in fetal and newborn (20- and 10-fold, respectively) than in adult kidneys. We conclude the following. 1) The fetal kidney expresses the renin gene. 2) Expression of the renin gene is subjected to developmental changes. 3) As maturation progresses, localization of renin synthesis and storage shifts from large intrarenal arteries to a restricted, classical juxtaglomerular site in the afferent arteriole.

Renin Gene Expression in Fetal Kidneys of Pregnancies Complicated by Twin-Twin Transfusion Syndrome

2001 ◽  
Vol 4 (2) ◽  
pp. 175-179 ◽  
Author(s):  
Mark D. Kilby ◽  
Craig Platt ◽  
Martin J. Whittle ◽  
Jill Oxley ◽  
George B.M. Lindop
Keyword(s):  
Gene Expression ◽  
Renal Cortex ◽  
Donor Kidney ◽  
Mortality And Morbidity ◽  
Renal Vasoconstriction ◽  
Unidirectional Flow ◽  
Renin Synthesis ◽  
Renin Gene ◽  
Renin Mrna ◽  
Fetal Urine

Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohydramnios. The disparities in amniotic fluid volumes represent differences in fetal urine output. These differences occur secondary to hemodynamic changes, in which the vascular arrangement of placental anastomoses in TTTS leads to unidirectional flow from the donor to the recipient twin. A better understanding of the pathophysiology may contribute to improved management of this morbid condition. We studied three consecutive prospectively diagnosed stillborn twin pairs affected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin anti-serum and with in situ hybridization using riboprobes complementary to renin mRNA, and renin-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli. The donor twin kidneys were smaller than those of the recipients, but the maturation of the renal cortex was not significantly different (28.2% immature glomeruli in the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic juxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [25th–75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs per 100 glomeruli; P < 0.05). In the donor kidney, increased renin release may, by a local action, contribute to renal vasoconstriction and oliguria. Increased renin and/or angiotensin II in the blood passing through the placental anastomoses may, by an endocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood flow and causing polyuria and polyhydramnios. These changes in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensating mechanism, the success of which may dictate the overall survival of the twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.

Developmental changes in renal renin mRNA half-life and responses to stimulation in fetal lambs

1999 ◽  
Vol 277 (4) ◽  
pp. R1130-R1135 ◽  
Author(s):  
Jinjuan Wang ◽  
James C. Rose
Keyword(s):  
Half Life ◽  
Cultured Cells ◽  
Primary Cultures ◽  
Perinatal Period ◽  
Fetal Life ◽  
Mrna Levels ◽  
Cortical Cells ◽  
Renin Gene ◽  
Renin Mrna ◽  
Immature Cells

In the perinatal period there is increased renin gene expression in the kidney compared with other stages of development. This may be related to changes in responsiveness of the renin gene to stimulation and/or differences in renin mRNA stability as development progresses. To ascertain if either responsiveness or stability changes in fetal life, we studied renin mRNA levels in primary cultures of renal cortical cells obtained from fetal lamb kidneys at two stages (0.7 and 0.9) of gestation after stimulation with isoproterenol, forskolin, or isobutyl methylxanthine and after inhibition of transcription with actinomycin D. Forskolin and isobutyl methylxanthine rapidly increased renin mRNA by at least twofold in the cultured cells from fetuses of both ages, with the sensitivity to stimulation higher in the cells from the mature fetal kidneys. Isoproterenol was effective only in mature fetal cells. In addition, the decay of renin mRNA after cessation of transcription was slower in mature cells compared with immature cells, the half-life being 11.6 ± 0.8 h in mature cells and 6.6 ± 0.6 h in immature cells ( P < 0.05). The data suggest that increases in both renin mRNA sensitivity to stimulation and in stability can contribute to the enhanced renin expression in the perinatal period.

A Widespread Abnormality of Renin Gene Expression in the Spontaneously Hypertensive Rat: Modulation in Some Tissues with the Development of Hypertension

1989 ◽  
Vol 77 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Nilesh J. Samani ◽  
John D. Swales ◽  
William J. Brammar
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Ribonuclease Protection

1. Renin messenger RNA (mRNA) levels were compared in the kidneys, livers, brains, adrenals, aortae and hearts of spontaneously hypertensive (SHR) and Wistar—Kyoto (WKY) rats at 5 and 12 weeks of age using a ribonuclease-protection technique 2. Relative levels of renin mRNA were increased in the kidney, liver, brain, adrenal and heart of the young SHR compared with the WKY. In the aorta, levels were similar in the two strains at 5 weeks 3. In 12-week-old animals, while increased levels persisted in the liver, brain and adrenal of the SHR, the level in the kidney was now the same in the two strains and the levels in the heart and aorta were lower in the SHR compared with the WKY 4. Renin mRNA levels in the kidneys of SHR and WKY were also compared by Northern blotting and confirmed the observations made with the ribonuclease-protection technique 5. The findings indicate a widespread abnormality of renin gene expression in the SHR which is modulated in some tissues by the development of hypertension 6. While the mechanism(s) for the abnormality remains to be determined, the increased renin mRNA levels in the SHR in several tissues concerned with blood pressure regulation suggests an important role for the renin-angiotensin system in the development and maintenance of hypertension 7. However, the finding of increased renin mRNA in the liver also suggests abnormalities in other, as yet unknown, functions of the renin—angiotensin system in the SHR.

Abstract 261: Endothelial Cells Contribute to RAS Activation in Microvascular Smooth Muscle Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kayoko Miyata ◽  
Ryousuke Satou ◽  
L Gabriel Navar
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Mrna Expression ◽  
Culture Medium ◽  
Primary Cultures ◽  
Mrna Levels ◽  
Ang Ii ◽  
Relative Ratio ◽  
Renin Mrna ◽  
Afferent Arterioles

Introduction: We have demonstrated that Ang II augments angiotensinogen (AGT) expression in rat preglomerular vascular smooth muscle cells (VSMCs). However, it is unclear if endothelial cells (ECs) are involved in augmentation of AGT in renal afferent arterioles. Hypothesis: We assessed the hypothesis that the ECs respond to paracrine signals that Ang II contribute to AGT augmentation in VSMCs. Objective: We established primary cultures of preglomerular ECs and examined the effects of Ang II and/or culture medium from ECs on AGT expression in preglomerular VSMCs. Methods and Results: We established primary cultures of preglomerular ECs, isolated from afferent arterioles of Sprague-Dawley rats. The cells were identified as ECs by being positive for a marker, CD34 and endothelial NOS and negative for alpha-SMA (a marker for VSMCs) and P4H-b (a marker for Fibroblasts) by immnostaining. The expression levels of AGT mRNA and renin mRNA in preglomerular ECs were examined by real-time RT-PCR. Ang II (100 pmol/L) increased AGT mRNA levels (1.34 +/- 0.16, by 100 pmol/L, N=4) and Renin mRNA levels (6.16 +/- 0.96, by 100 nmol/L, N=4) in ECs. On the other hand, the same dose of Ang II suppressed Renin mRNA expression in isolated Juxtaglomerular cells (JGs). These results indicate that preglomerular ECs are respond to Ang II and exclude the possible contamination of JGs into ECs. 100 pmol/L of Ang II increased AGT mRNA expression levels (1.37 +/- 0.03, relative ratio, N=4) in preglomerular VSMCs and the culture medium of ECs without Ang II treatment also more increased AGT mRNA expression (1.62 +/- 0.13, relative ratio, N=4) in preglomerular VSMCs. The AGT mRNA expression augmentation was enhanced when preglomerular VSMCs were treated with culture medium of Ang II-treated preglomerular ECs (2.39 +/- 0.41, relative ratio, N=4). The synergistic effects of Ang II and preglomerular ECs were also observed in PAI-1 expression in preglomerular VSMCs. Conclusion: These data demonstrate that preglomerular ECs contribute to Ang II-upregulation of AGT in renal afferent arterioles leading to further Ang II augmentation, which leads to increases in inflammatory and sclerotic factors in preglomerular VSMCs.

Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney

1993 ◽  
Vol 264 (4) ◽  
pp. R696-R702 ◽  
Author(s):  
A. Tufro-McReddie ◽  
R. L. Chevalier ◽  
A. D. Everett ◽  
R. A. Gomez
Keyword(s):  
Gene Expression ◽  
Aortic Coarctation ◽  
Perfusion Pressure ◽  
Receptor Gene ◽  
At1 Receptor ◽  
Northern Analysis ◽  
Renin Gene ◽  
Renin Mrna ◽  
Receptor Gene Expression

To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

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