Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

Rasch, Ruth; Jensen, Boye L.; Nyengaard, Jens Randel; Skøtt, Ole

doi:10.1007/s004410051085

Cited by 26 publications

(30 citation statements)

References 19 publications

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“…This finding suggests that salt balance regulates steady-state renin production mainly by modulating the number of renin-producing cells rather than by graded upand downregulation of renin gene transcription within individual cells. Although an altered expression per cell cannot be excluded, the assumption of such an "all or none" state of renin expression is in good accordance with previous studies (11,31). Thus salt balance appears to regulate renin expression primarily by inhibiting or stimulating the phenotype switch of renin precursor cells (myofibroblasts, smooth muscle cells) into renin-producing cells (34).…”

Section: Discussionsupporting

confidence: 88%

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Machura

Neubauer

Steppan

et al. 2012

American Journal of Physiology-Renal Physiology

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The salt intake of an organism controls the number of renin-producing cells in the kidney by yet undefined mechanisms. This study aimed to assess a possible mediator role of preglomerular blood pressure in the control of renin expression by oral salt intake. We used wild-type (WT) mice and mice lacking angiotensin II type 1a receptors (AT 1aϪ/Ϫ) displaying an enhanced salt sensitivity to renin expression. In WT kidneys, we found renin-expressing cells at the ends of all afferent arterioles. A low-salt diet (0.02%) led to a moderate twofold increase in reninexpressing cells along afferent arterioles. In AT 1aϪ/Ϫ mice, lowering of salt content led to a 12-fold increase in renin expression. Here, the renin-expressing cells were distributed along the preglomerular vascular tree in a typical distal-to-proximal distribution gradient which was most prominent at high salt intake and was obliterated at low salt intake by the appearance of renin-expressing cells in proximal parts of the preglomerular vasculature. While lowering of salt intake produced only a small drop in blood pressure in WT mice, the marked reduction of systolic blood pressure in AT 1aϪ/Ϫ mice was accompanied by the disappearance of the distribution gradient from afferent arterioles to arcuate arteries. Unilateral renal artery stenosis in AT 1aϪ/Ϫ mice on a normal salt intake produced a similar distribution pattern of reninexpressing cells as did low salt intake. Conversely, increasing blood pressure by administration of the NOS inhibitor N-nitro-L-arginine methyl ester or of the adrenergic agonist phenylephrine in AT1aϪ/Ϫ mice kept on low salt intake produced a similar distribution pattern of renin-producing cells as did normal salt intake alone. These findings suggest that changes in preglomerular blood pressure may be an important mediator of the influence of salt intake on the number and distribution of renin-producing cells in the kidney. AT1a knockoutTHE MAINTENANCE OF SALT HOMEOSTASIS is a central function of the renin-angiotensin-system. A threat to salt balance leads to compensatory changes in renin expression in the kidney in a way that the number of renin-expressing cells increases during salt deficiency and decreases during salt overload (41). It is assumed that the salt-related changes in renin-expressing cells in the kidney are not caused by cell proliferation or apoptosis, but instead result from reversible phenotype changes of preglomerular smooth muscle cells into renin-producing cells and vice versa (34). The intracellular signaling pathways defining the specific phenotype of these cells are yet unknown. Furthermore, it is unclear by which mechanisms salt balance controls the number of renin-producing cells. It has been suggested that the effects of salt balance may affect renin expression in the preglomerular afferent arterioles by autacoids such as nitric oxide (NO) or prostaglandins (42) since salt intake has been shown to control the juxtaglomerular expression of cyclooxygenase-2 (COX-2) (17) and nitric oxide synthase-1 (NOS-1) (37...

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Section: Discussionsupporting

confidence: 88%

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Machura

Neubauer

Steppan

et al. 2012

American Journal of Physiology-Renal Physiology

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“…For example, in rats under normal laboratory conditions, one renin granule is found, on average, in a cell volume of 5 m 3 (715,813). A very similar density was observed during chronic salt depletion when the overall renin synthesis and secretion are strongly stimulated.…”

Section: Renin Secretory Vesiclesmentioning

confidence: 67%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

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The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).

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“…The A 1 R is a G i -coupled receptor whose binding leads to activation of phospholipase C, increasing intracellular calcium (28,29). Because JG cells appear in the afferent arteriole (45,60,70) contiguous to the vascular smooth muscle, it is likely that A 1 R activation also increases intracellular calcium in JG cells, inhibiting cAMP formation and blunting renin release (50 -53). This is consistent with our finding that JG cell A 1 R activation inhibits renin release through a calcium channel-mediated pathway, in our demonstration that increases in both extracellular and intracellular calcium were required for the A 1 R inhibition of renin.…”

Section: Discussionmentioning

confidence: 99%

Adenosine inhibits renin release from juxtaglomerular cells via an A₁ receptor-TRPC-mediated pathway

Ortiz-Capisano

Atchison

Harding

et al. 2013

American Journal of Physiology-Renal Physiology

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Ortiz-Capisano MC, Atchison DK, Harding P, Lasley RD, Beierwaltes WH. Adenosine inhibits renin release from juxtaglomerular cells via an A 1 receptor-TRPC-mediated pathway. Am J Physiol Renal Physiol 305: F1209 -F1219, 2013. First published July 24, 2013 doi:10.1152/ajprenal.00710.2012.-Renin is synthesized and released from juxtaglomerular (JG) cells. Adenosine inhibits renin release via an adenosine A 1 receptor (A1R) calcium-mediated pathway. How this occurs is unknown. In cardiomyocytes, adenosine increases intracellular calcium via transient receptor potential canonical (TRPC) channels. We hypothesized that adenosine inhibits renin release via A 1R activation, opening TRPC channels. However, higher concentrations of adenosine may stimulate renin release through A 2R activation. Using primary cultures of isolated mouse JG cells, immunolabeling demonstrated renin and A 1R in JG cells, but not A2R subtypes, although RT-PCR indicated the presence of mRNA of both A 2AR and A2BR. Incubating JG cells with increasing concentrations of adenosine decreased renin release. Different concentrations of the adenosine receptor agonist N-ethylcarboxamide adenosine (NECA) did not change renin. Activating A 1R with 0.5 M N6-cyclohexyladenosine (CHA) decreased basal renin release from 0.22 Ϯ 0.05 to 0.14 Ϯ 0.03 g of angiotensin I generated per milliliter of sample per hour of incubation (AngI/ml/mg prot) (P Ͻ 0.03), and higher concentrations also inhibited renin. Reducing extracellular calcium with EGTA increased renin release (0.35 Ϯ 0.08 g AngI/ml/mg prot; P Ͻ 0.01), and blocked renin inhibition by CHA (0.28 Ϯ 0.06 g AngI/ml/mg prot; P Ͻ 0. 005 vs. CHA alone). The intracellular calcium chelator BAPTA-AM increased renin release by 55%, and blocked the inhibitory effect of CHA. Repeating these experiments in JG cells from A 1R knockout mice using CHA or NECA demonstrated no effect on renin release. However, RT-PCR showed mRNA from TRPC isoforms 3 and 6 in isolated JG cells. Adding the TRPC blocker SKF-96365 reversed CHA-mediated inhibition of renin release. Thus A 1R activation results in a calcium-dependent inhibition of renin release via TRPC-mediated calcium entry, but A 2 receptors do not regulate renin release. renin; adenosine; calcium; A 1R; CHA; adenosine receptors; transient receptor potential canonical RENIN IS PRODUCED BY, STORED in, and released from juxtaglomerular (JG) cells located in the lamina media of the afferent arteriole at the entrance to the glomerulus (7, 31). Two main intracellular second-messenger systems are known to regulate renin secretion: stimulation of renin release by the cyclic nucleotide cAMP; and inhibition or renin secretion by increased intracellular calcium (1-3, 16, 25, 30).Adenosine is a purine nucleoside catabolite of ATP. Adenosine's effects are mediated by the activation of four G protein-coupled receptor (GPCR) subtypes: A 1 , A 2A , A 2B , and A 3 (13, 44). Adenosine inhibits renin secretion in vivo and in vitro (9, 37). It is considered that adenosine from the macula densa inhib...

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Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

Cited by 26 publications

References 19 publications

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Physiology of Kidney Renin

Adenosine inhibits renin release from juxtaglomerular cells via an A₁ receptor-TRPC-mediated pathway

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Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

Cited by 26 publications

References 19 publications

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Role of blood pressure in mediating the influence of salt intake on renin expression in the kidney

Physiology of Kidney Renin

Adenosine inhibits renin release from juxtaglomerular cells via an A1 receptor-TRPC-mediated pathway

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Product

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Adenosine inhibits renin release from juxtaglomerular cells via an A₁ receptor-TRPC-mediated pathway