Inhibition of heme oxygenase decreases sodium and fluid absorption in the loop of Henle

2003 ◽  
Vol 285 (3) ◽  
pp. F484-F490 ◽  
Author(s):  
Tong Wang ◽  
Hyacinth Sterling ◽  
Wei A. Shao ◽  
QingShang Yan ◽  
Matthew A. Bailey ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Heme Oxygenase ◽  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Fluid Absorption ◽  
High K ◽  
Normal Chow ◽  
Normal Rat

We previously demonstrated that carbon monoxide (CO) stimulates the apical 70-pS K+ channel in the thick ascending limb (TAL) of the rat kidney (Liu HJ, Mount DB, Nasjletti A, and Wang WH. J Clin Invest 103: 963-970, 1999). Because the apical K+ channel plays a key role in K+ recycling, we tested the hypothesis that heme oxygenase (HO)-dependent metabolites of heme may affect Na+ transport in the TAL. We used in vivo microperfusion to study the effect of chromium mesoporphyrin (CrMP), an inhibitor of HO, on fluid absorption ( Jv) and Na+ absorption ( JNa) in the loop of Henle and renal clearance methods to examine the effect of CrMP on renal sodium excretion. Microperfusion experiments demonstrated that addition of CrMP to the loop of Henle decreased Jv by 13% and JNa by 20% in animals on normal rat chow and caused a decrease in Jv (39%) and JNa (40%) in rats on a high-K+ (HK) diet. The effect of CrMP is the result of inhibition of HO because addition of MgPP, an analog of CrMP that does not inhibit HO, had no effect on Jv. Western blot analysis showed that HO-2 is expressed in the kidney and that the level of HO-2 was significantly elevated in animals on a HK diet. Renal clearance studies demonstrated that the infusion of CrMP increased the excretion of urinary Na+ (ENa) and volume (UV) without changes in glomerular filtration rate. The effect of CrMP on ENa and UV was larger in HK rats than those kept on normal chow. We conclude that HK intake increases HO-2 expression in the kidney and that HO-dependent metabolites of heme, presumably CO, play a significant role in the regulation of Na+ transport in the loop of Henle.

ADH-like effects of calcitonin on electrolyte transport by Henle's loop of rat kidney

1984 ◽  
Vol 246 (2) ◽  
pp. F213-F220 ◽  
Author(s):  
J. M. Elalouf ◽  
N. Roinel ◽  
C. de Rouffignac
Keyword(s):  
Rat Kidney ◽  
Phosphate Transport ◽  
Hormonal Control ◽  
Electrolyte Transport ◽  
Human Calcitonin ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
The One ◽  
In Vivo Administration

The effects of physiological doses of human calcitonin (HCT) on renal excretion and tubular transport of water and electrolytes were investigated in hormone-deprived rats, i.e., homozygous DI Brattleboro rats with reduced levels of circulating glucagon, parathyroid hormone, and thyrocalcitonin, as these hormones are believed, together with ADH, to stimulate the same cells of the thick ascending limb. The experimental design was similar to the one used in a preceding study aimed at determining the effects of ADH in hormone-deprived rats [C. de Rouffignac et al. Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F156-F164, 1983]. In the present experiments, HCT consistently increased the reabsorption of Mg, Ca, and K and, to a lesser extent, Na and Cl in the loop of Henle, but phosphate transport did not rise. The urinary excretion rate of Mg and Ca fell significantly. These data are very similar to the findings obtained with ADH on hormone-deprived rats. It is concluded that, in vivo, administration of HCT 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, and 2) consistently enhances Mg and Ca reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle. The similarity of the physiological responses elicited by ADH and calcitonin on the thick ascending limb supports the hypothesis of multiple hormonal control of electrolyte transport by the thick ascending limb.

Calcium transport in the proximal convoluted tubule and loop of Henle of rats made diabetic with streptozotocin

1991 ◽  
Vol 131 (3) ◽  
pp. 373-380 ◽  
Author(s):  
H. O. Garland ◽  
P. J. Harris ◽  
T. O. Morgan
Keyword(s):  
Calcium Absorption ◽  
Diabetic Rats ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Fluid Absorption ◽  
New Information ◽  
Causative Factors ◽  
Nephron Segment ◽  
Acute Changes

ABSTRACT In-vivo microperfusion was used to localize the reabsorptive defect responsible for the hypercalciuria of diabetes mellitus and to investigate possible causative factors. Unidirectional proximal calcium absorption was not significantly different in rats made diabetic with streptozotocin compared with controls, providing evidence against the involvement of this nephron segment in the phenomenon. Calcium absorption by the loop of Henle, was however, significantly (P<0·01) lower in diabetic animals (32·1 ±1·2 vs 40·4±0·6 pmol/min). Based on our knowledge of calcium movements within the loop, it is likely that the reabsorptive defect resides within the thick ascending limb. The calcium lesion was found to be independent of acute changes in intraluminal glucose concentration and could not be corrected by acute insulin treatment. The study also provides new information on the relationship between intratubular glucose and fluid movements in the rat nephron. In diabetic rats a proximal perfusate containing 30 mmol glucose/l resulted in fluid absorption comparable with that seen in control rats perfused with 5 mmol glucose/l. However, intraluminal glucose had a stimulatory effect on fluid absorption in the loop of Henle of diabetic rats (10·7 ±0·5 vs 7·9±0·4 nl/min; P<0·01). Journal of Endocrinology (1991) 131, 373–380

Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney

1983 ◽  
Vol 244 (2) ◽  
pp. F156-F164 ◽  
Author(s):  
C. de Rouffignac ◽  
B. Corman ◽  
N. Roinel
Keyword(s):  
Rat Kidney ◽  
Phosphate Transport ◽  
Urinary Flow ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Proximal Tubular ◽  
Tubular Flow ◽  
Excretion Rates ◽  
In Vivo Administration

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on renal excretion and tubular transport of water and electrolytes were investigated in homozygous DI Brattleboro rats. To ascertain these effects on the loop of Henle, circulating glucagon, parathyroid hormone, and thyrocalcitonin were reduced before the experiments, as these hormones are believed to stimulate the same cells of the thick ascending limb as ADH. dDAVP did not alter either glomerular or proximal tubular functions. In the loop, it consistently raised reabsorption of Mg, Ca, K, and, to a lesser extent, Na and Cl, but phosphate transport was not affected. dDAVP lowered the urinary excretion rates for Mg, Ca, K, Cl, and total solutes. For Mg, this reduction was independent of the drop in the urinary flow rate following dDAVP administration but was significantly correlated to this drop in the case of Ca, K, Cl, and total solutes. Na and P excretions were not altered by dDAVP. It is concluded that, in vivo, administration of ADH 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, 2) consistently enhances Mg reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle, and 3) at maximal antidiuresis, raises Ca, K, Cl, and total solute reabsorption, probably because of the drop in tubular flow rates in the distal parts of the nephron consequent to the hormone administration.

Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1

1996 ◽  
Vol 271 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
C. A. Ecelbarger ◽  
J. Terris ◽  
J. R. Hoyer ◽  
S. Nielsen ◽  
J. B. Wade ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Rat Colon ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Water Excretion ◽  
Saline Loading ◽  
Cloned Cdna ◽  
Urinary Concentrating Ability

To investigate the role of the thick ascending limb (TAL) Na(+)-K(+)-2Cl- cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed "NKCC-2"). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na(+)-K(+)-2Cl- cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na(+)-K(+)-2Cl- transporter and demonstrate that the expression of this transporter is regulated.

Functional Expression of Human Heme Oxygenase-1 Gene in Renal Structure of Spontaneously Hypertensive Rats

2003 ◽  
Vol 228 (5) ◽  
pp. 454-458 ◽  
Author(s):  
Alvin I. Goodman ◽  
Shou Quan ◽  
Liming Yang ◽  
Arika Synghal ◽  
Nader G. Abraham
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Spontaneously Hypertensive Rats ◽  
Rat Kidney ◽  
Functional Expression ◽  
Heme Oxygenase 1 ◽  
Thick Ascending Limb ◽  
Bile Pigments ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Heme oxygenase (HO), by catabolizing heme to bile pigments, regulates the levels and activity of cellular hemoprotein and HO activity. We examined the effect of delivery of the human HO-1 gene on cellular heme in renal tissue using a retroviral vector. We used a single intracardiac injection of the concentrated infectious viral particles in 5-day-old spontaneously hypertensive rats; 25 were transduced with empty vector and 25 were transduced with the human HO-1 gene. Functional expression of human and rat HO-1 was measured after 2 and 4 weeks. Reverse transcription polymerase chain reaction showed that human HO-1 mRNA was expressed as early as 2 weeks, with the highest levels in the kidney. Western blot analysis showed distribution of human HO-1 protein in rat kidney structures, predominantly in the thick ascending limb of the loop of Henle as well as in proximal tubules and preglomerular arterioles. These areas also demonstrated higher HO activity as measured by increased conversion of heme to bilirubin and carbon monoxide. Functional expression of the human HO-1 gene was associated with a decrease in blood pressure in 4- and 8-week-old spontaneously hypertensive rats. Compared with nontransduced rats, human HO-1 gene overexpression in transduced rats was associated with a 35% decrease in urinary 20-hydroxyeicosatetraenoic acid, a potent vasoconstrictor and an inhibitor of tubular Na+ transport, which may be related to the decrease in blood pressure.

PKC-dependent superoxide production by the renal medullary thick ascending limb from diabetic rats

2009 ◽  
Vol 297 (5) ◽  
pp. F1220-F1228 ◽  
Author(s):  
Jing Yang ◽  
Pascale H. Lane ◽  
Jennifer S. Pollock ◽  
Pamela K Carmines
Keyword(s):  
Rat Kidney ◽  
Diabetic Rats ◽  
Thick Ascending Limb ◽  
Protein Levels ◽  
Medullary Thick Ascending Limb ◽  
Pkc Isoforms ◽  
Normal Rat ◽  
Membrane Bound ◽  
Pkc Activation

Type 1 diabetes (T1D) is a state of oxidative stress accompanied by PKC activation in many tissues. The primary site of O2•− production by the normal rat kidney is the medullary thick ascending limb (mTAL). We hypothesized that T1D increases O2•− production by the mTAL through a PKC-dependent mechanism involving increased expression and translocation of one or more PKC isoforms. mTAL suspensions were prepared from rats with streptozotocin-induced T1D (STZ mTALs) and from normal or sham rats (normal/sham mTALs). O2•− production by STZ mTALs was fivefold higher than normal/sham mTALs ( P < 0.05). PMA (30 min) mimicked the effect of T1D on O2•− production. Exposure to calphostin C or chelerythrine (PKC inhibitors), Gö6976 (PKCα/β inhibitor), or rottlerin (PKCδ inhibitor) decreased O2•− production to <20% of untreated baseline in both normal/sham and STZ mTALs. PKCβ inhibitors had no effect. PKC activity was increased in STZ mTALs ( P < 0.05 vs. normal/sham mTALs) and was unaltered by antioxidant exposure (tempol). PKCα protein levels were increased by 70% in STZ mTALs, with a ∼30% increase in the fraction associated with the membrane (both P < 0.05 vs. sham). PKCβ protein levels were elevated by 29% in STZ mTALs ( P < 0.05 vs. sham) with no change in the membrane-bound fraction. Neither PKCδ protein levels nor its membrane-bound fraction differed between groups. Thus STZ mTALs display PKC activation, upregulation of PKCα and PKCβ protein levels, increased PKCα translocation to the membrane, and accelerated O2•− production that is eradicated by inhibition of PKCα or PKCδ (but not PKCβ). We conclude that increased PKCα expression and activity are primarily responsible for PKC-dependent O2•− production by the mTAL during T1D.

scholarly journals In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

2010 ◽  
Vol 299 (6) ◽  
pp. F1473-F1485 ◽  
Author(s):  
Daniel Ackermann ◽  
Nikolay Gresko ◽  
Monique Carrel ◽  
Dominique Loffing-Cueni ◽  
Daniel Habermehl ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Glucocorticoid Receptors ◽  
Nuclear Translocation ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Plasma Aldosterone ◽  
Thick Ascending Limb ◽  
Cell Nuclei

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.

Localization of kallikrein in the rat kidney and its anatomical relationship to renin.

1982 ◽  
Vol 30 (4) ◽  
pp. 385-390 ◽  
Author(s):  
T B Orstavvik ◽  
T Inagami
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Juxtaglomerular Apparatus ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Afferent Arteriole ◽  
Epitheloid Cells ◽  
Anatomical Relationship

The anatomical relationship between kallikrein and renin in the rat kidney was investigated immunohistochemically by the peroxidase-antiperoxidase method. Kallikrein was localized to the convoluted distal tubule, starting at a point, distal to the juxtaglomerular apparatus, where the thick ascending limb of loop of Henle transformed into the convoluted distal tubule. The thick ascending limb was identified by its content of uromucoid (Tamm-Horsfall glycoprotein). Kallikrein was never observed within the juxtaglomerular apparatus itself. The kallikrein-containing tubule ended where the distal tubule submerged into the collecting duct. Renin was found in epitheloid cells of the afferent arteriole. When neighboring sections were stained for kallikrein and renin, respectively, no close anatomical relationship was observed between the kallikrein-containing and the renin-containing structures.

scholarly journals 3′-Untranslated regions of oxidative phosphorylation mRNAs function in vivo as enhancers of translation

2000 ◽  
Vol 352 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Carlo M. Di LIEGRO ◽  
Marianna BELLAFIORE ◽  
José M. IZQUIERDO ◽  
Anja RANTANEN ◽  
José M. CUEZVA
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Fluorescent Protein ◽  
Rat Kidney ◽  
In Vitro Translation ◽  
Mitochondrial Transcription Factor ◽  
Normal Rat ◽  
Green Fluorescent

Recent findings have indicated that the 3´-untranslated region (3´-UTR) of the mRNA encoding the β-catalytic subunit of the mitochondrial H+-ATP synthase has an in vitro translation-enhancing activity (TEA) [Izquierdo and Cuezva, Mol. Cell. Biol. (1997) 17, 5255–5268; Izquierdo and Cuezva, Biochem. J. (2000) 346, 849–855]. In the present work, we have expressed chimaeric plasmids that encode mRNA variants of green fluorescent protein in normal rat kidney and liver clone 9 cells to determine whether the 3´-UTRs of nuclear-encoded mRNAs involved in the biogenesis of mitochondria have an intrinsic TEA. TEA is found in the 3´-UTR of the mRNAs encoding the α- and β-subunits of the rat H+-ATP synthase complex, as well as in subunit IV of cytochrome c oxidase. No TEA is present in the 3´-UTR of the somatic mRNA encoding rat mitochondrial transcription factor A. Interestingly, the TEA of the 3´-UTR of mRNAs of oxidative phosphorylation is different, depending upon the cell type analysed. These data provide the first in vivo evidence of a novel cell-specific mechanism for the control of the translation of mRNAs required in mitochondrial function.

scholarly journals Cloning, renal distribution, and regulation of the rat Na+- HCO 3 − cotransporter

1998 ◽  
Vol 274 (6) ◽  
pp. F1119-F1126 ◽  
Author(s):  
Charles E. Burnham ◽  
Michael Flagella ◽  
Zhaohui Wang ◽  
Hassane Amlal ◽  
Gary E. Shull ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Rat Kidney ◽  
Human Kidney ◽  
Cloning And Expression ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Reading Frame ◽  
Medullary Thick Ascending Limb ◽  
Nephron Segment

We recently reported the cloning and expression of a human kidney Na+-[Formula: see text]cotransporter (NBC-1) (C. E. Burnham, H. Amlal, Z. Wang, G. E. Shull, and M. Soleimani. J. Biol. Chem. 272: 19111–19114, 1997). To expedite in vivo experimentation, we now report the cDNA sequence of rat kidney NBC-1. In addition, we describe both the organ and nephron segment distributions and the regulation of NBC-1 mRNA under three models of pH stress: chloride-depletion alkalosis (CDA), metabolic acidosis, and bicarbonate loading. Rat NBC-1 cDNA encodes an open reading frame of 1,035 amino acids, with 96 and 87% identity to human and salamander NBC-1, respectively. Rat NBC-1 mRNA is expressed at high levels in kidney and brain, with lower levels in colon, stomach, and heart. None appears in liver. In the kidney, NBC-1 is expressed mainly in the proximal tubule, with traces found in medullary thick ascending limb and papilla. [Formula: see text] loading decreased NBC-1 mRNA levels, which were unchanged either by metabolic acidosis or by CDA.

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