Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.

Vernace, Melchiore A.; Mento, P. F.; Maita, Masashi; Girardi, Erika; Chang, Mei; Nord, Edward P.; Wilkes, Barry M.

doi:10.1172/jci118019

Cited by 13 publications

(10 citation statements)

References 32 publications

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“…Based on our data, we propose that urinary ir-ET-l levels in rats with reduced renal mass reflect ET-1 overproduction in preglomcrular arteries and glomeruli. This hypothesis is in keeping with recent studies showing that increased glomerular ET-1 production in glomerulonephritis induced a concomitant rise in urinary ET-I excretion [35], However, we cannot exclude the possi bility that urinary ET-1 derives from the inner medullary collecting duet (IMCD) epithelial cells and medullary in terstitial cells [36,37]. Although we found lower ir-ET-l concentration in the renal papilla of uremic rats, it remained significantly high compared to other renal tissues.…”

Section: Discussionsupporting

confidence: 80%

“…Under normal conditions. ET-1 plays an important role in blood volume regulation through its inhibitory effects on Na7K -ATPase activity and on vasopressin-induced water reabsorption in IMCD [38,39], ET-1 production in IMCD epithelial and medullary interstitial cells is normally in duced by hyperosmolar conditions [36,37]. In chronic renal failure, however, medullary osmolality is reduced, thus at tenuating ET-1 production.…”

Section: Discussionmentioning

confidence: 99%

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Increased Immunoreactive Endothelin-1 Levels in Blood Vessels and Glomeruli of Rats with Reduced Renal Mass

Lariviere¹,

D’Amours²,

Lebel

et al. 1997

Kidney Blood Press Res

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Elevated plasma and urinary endothelin-1 (ET-1) levels have been reported in patients with renal failure as well as in remnant kidney models of chronic renal failure. We investigated whether these changes are related to increased ET-1 production in cardiovascular and renal tissues of rats with reduced renal mass. In uremic rats, systolic blood pressure rose in parallel with the progression of renal insufficiency. At week 6, changes in systolic blood pressure were positively correlated with serum creatinine levels (r = 0.728, p < 0.01). Plasma immunoreactive ET-1 (ir-ET-1) concentration was similar in uremic rats and sham-operated controls. In contrast, urinary ir-ET-1 excretion was significantly greater in uremic rats and was correlated with the elevation of serum creatinine and proteinuria (r = 0.795, and 0.922, p < 0.01, respectively). Compared to the controls, ir-ET-1 concentration in the thoracic aorta, preglomerular arteries and glomeruli were 1.4-, 3.5- and 6.7-fold higher, respectively, in uremic rats (p < 0.01) than in the controls. However, ir-ET-1 concentration in the mesenteric arterial bed and the left ventricle remained similar in the 2 groups, whereas it was significantly lower in the renal papilla of uremic rats (p < 0.01). Thus, ET-1 production is unchanged or slightly increased in extrarenal cardiovascular tissues of rats with reduced renal mass. In contrast, ET-1 production is significantly augmented in preglomerular arteries and glomeruli, but reduced in the papilla, suggesting that increased urinary ir-ET-1 excretion in uremic rats reflects ET-1 overproduction in the former renal tissues. Elevated ET-1 production in blood vessels and glomeruli may thus play a key role in the aggravation of hypertension and the progression of renal insufficiency in this rat remnant kidney model of chronic renal failure.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Increased Immunoreactive Endothelin-1 Levels in Blood Vessels and Glomeruli of Rats with Reduced Renal Mass

Lariviere¹,

D’Amours²,

Lebel

et al. 1997

Kidney Blood Press Res

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“…(B-G are from Kaissling and Le Hir 1994i the volume of the interstitium (Hughes AK et al 1995). Finally, they produce vasodepressant lipids, in particular PGE2 (Zusman and Keiser 1977;Muirhead 1990Muirhead , 1991Vernace et al 1995). These may affect not only the renomedullary hemodynamics, but also, in an autocrine pathway, the contractility of the interstitial cells themselves (Hughes AK et al 1995).…”

Section: Medullary Interstitiummentioning

confidence: 99%

Morphology of interstitial cells in the healthy kidney

et al. 1996

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Renal interstitial cells play an important role in renal function and renal diseases. We describe the morphology of renal interstitial cells in the healthy kidney. We distinguish within the renal interstitium (1) renal fibroblasts and (2) cells of the immune system. Fibroblasts are in the majority and constitute the scaffold of the kidney; they are interconnected by junctions, and are attached to tubules and vessels. Although the phenotype of fibroblasts shows some variation depending on their location in the kidney and on their functional stage, their recognition as fibroblasts is possible on account of structural features. Among the cell types of the second group, antigen-presenting dendritic cells are the most abundant in in the peritubular interstitial spaces of healthy kidneys. Their incidence is highest in the inner stripe of the outer medulla. They share some morphological features with fibroblasts but lack others--junctional complexes, morphologically defined connections with tubules and vessels, and the prominent layer of actin filaments under the plasma membrane--that are characteristic for fibroblasts. Dendritic cells in healthy kidneys are morphologically different from macrophages, which are characterized by abundant primary and secondary lysosomes. In healthy kidneys macrophages are restricted to the connective tissue of the renal capsule and the pelvic wall, and to the periarterial connective tissue. Lymphocytes are rare in healthy kidneys. The distinction of cell types by morphology is supported by differences of membrane proteins. Among all interstitial cells in the renal cortex, fibroblasts alone exhibit ecto-5'-nucleotidase. Dendritic cells constitutively have a high abundance of MHC class II protein. Both proteins are mutually exclusive. Rat macrophages display the membrane antigen ED 2 and lymphocytes exhibit specific surface antigens, depending on their type and functional stage, e.g., CD4 or CD8.

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“…Others have also noted differences in the expression of vasoactive peptide receptors by osmolality. Vernace et al (30) have reported a reduction in endothelin binding to its ET A receptor in cultured RMICs. In contrast, in cultured inner medullary collecting duct cells, which like RMICs, are commonly exposed to high extracellular tonicity in the renal medulla, high osmolality stimulates atrial natriuretic peptide A receptor activity and gene expression (3).…”

Section: Discussionmentioning

confidence: 97%

Posttranscriptional mechanisms contribute to osmotic regulation of ANG type 1 receptors in cultured rat renomedullary interstitial cells

Lee

Wu²,

Sandberg³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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showed that ANG II receptors in cultured rat renomedullary interstitial cells (RMICs) are osmotically regulated (19). The current study examined the mechanisms underlying this osmotic regulation in RMICs cultured in isoosmotic (300 mosmol/kgH 2O) and hyperosmotic (600 mosmol/kgH2O) conditions. Radioligand competition analysis coupled with RNase protection assays (RPA) and ligandmediated receptor internalization studies revealed that RMICs primarily express the type 1a angiotensin receptor (AT 1aR). When cultured under hyperosmotic conditions, the density (B max) of AT1R in RMIC membranes decreased by 31% [B max (pmol/mg protein): 300 mosmol/ kgH 2O, 6.44 Ϯ 0.46 vs. 600 mosmol/kgH2O, 4.42 Ϯ 0.37, n ϭ 8, P Ͻ 0.01], under conditions in which no detectable changes in AT 1aR mRNA expression or in the kinetics of ligand-mediated AT 1R internalization were observed. RNA electromobility shift assays showed that RNA protein complex (RPC) formation between RMIC cytosolic RNA binding proteins and the 5Ј leader sequence (5ЈLS) of the AT 1aR was increased 1.5-fold under hyperosmotic conditions [5ЈLS RPC (arbitrary units): 300 mosmol/kgH 2O, 0.79 Ϯ 0.08 vs. 600 mosmol/ kgH 2O, 1.17 Ϯ 0.07, n ϭ 4, P Ͻ 0.01]. These results suggest that the downregulation of AT 1aR expression in RMICs cultured under hyperosmotic conditions is regulated at the posttranscriptional level by RNA binding proteins that interact within the 5ЈLS of the AT 1aR mRNA. The downregulation of AT 1aR expression under hyperosmotic conditions may be an important mechanism by which the activity of ANG II is regulated in the hyperosmotic renal medulla. angiotensin II; angiotensin receptors; osmolality; posttranscriptional regulation; RNA binding proteins THE RENIN-ANGIOTENSIN SYSTEM (RAS) plays an important role in regulating systemic blood pressure and fluid and electrolyte balance (4, 21). Although more than one peptide has thus far been reported to mediate the physiological action of the RAS in the kidney (1), still to date, the main active peptide of the RAS is ANG II. ANG II mediates its actions through a number of receptor subtypes; however, the majority of its actions are mediated through the AT 1 receptor subtype (AT 1 R). In the kidney, AT 1 Rs are widely distributed: they are localized to cortical mesangial cells and proximal tubules (11) and renomedullary interstitial cells (RMICs) (35). Given the localization of AT 1 Rs in both the renal cortex and medulla, we do not commonly think that the mechanisms that regulate their expression and activity may be different. As a result of functional urine-concentrating mechanisms, renal medullary cells are normally exposed to very high extracellular concentrations of NaCl (6). It is thus conceivable that these constant fluctuations in extracellular osmolality will affect the activity of ANG II and will contribute to the regulation of its cell surface receptor. To date, very little is known about the osmotic regulation of AT 1 Rs in the renal medulla.

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Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.

Cited by 13 publications

References 32 publications

Increased Immunoreactive Endothelin-1 Levels in Blood Vessels and Glomeruli of Rats with Reduced Renal Mass

Increased Immunoreactive Endothelin-1 Levels in Blood Vessels and Glomeruli of Rats with Reduced Renal Mass

Morphology of interstitial cells in the healthy kidney

Posttranscriptional mechanisms contribute to osmotic regulation of ANG type 1 receptors in cultured rat renomedullary interstitial cells

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