scholarly journals Angiotensin II inhibits NaCl absorption in the rat medullary thick ascending limb

2004 ◽  
Vol 287 (3) ◽  
pp. F404-F410 ◽  
Author(s):  
Nicolas Lerolle ◽  
Soline Bourgeois ◽  
Françoise Leviel ◽  
Gaëtan Lebrun ◽  
Michel Paillard ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Plasma Membranes ◽  
Inhibitory Effect ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Nacl Absorption ◽  
Medullary Thick Ascending Limb

NaCl reabsorption in the medullary thick ascending limb of Henle (MTALH) contributes to NaCl balance and is also responsible for the creation of medullary interstitial hypertonicity. Despite the presence of angiotensin II subtype 1 (AT1) receptors in both the luminal and the basolateral plasma membranes of MTALH cells, no information is available on the effect of angiotensin II on NaCl reabsorption in MTALH and, furthermore, on angiotensin II-dependent medullary interstitial osmolality. MTALHs from male Sprague-Dawley rats were isolated and microperfused in vitro; transepithelial net chloride absorption ( JCl) as well as transepithelial voltage ( Vte) were measured. Luminal or peritubular 10−11 and 10−10 M angiotensin II had no effect on JCl or Vte. However, 10−8 M luminal or peritubular angiotensin II reversibly decreased both JCl and Vte. The effect of both luminal and peritubular angiotensin II was prevented by the presence of losartan (10−6 M). By contrast, PD-23319, an AT2-receptor antagonist, did not alter the inhibitory effect of 10−8 M angiotensin II. Finally, no additive effect of luminal and peritubular angiotensin II was observed. We conclude that both luminal and peritubular angiotensin II inhibit NaCl absorption in the MTALH via AT1 receptors. Because of intrarenal angiotensin II synthesis, angiotensin II concentration in medullary tubular and interstitial fluids may be similar in vivo to the concentration that displays an inhibitory effect on NaCl reabsorption under the present experimental conditions.

scholarly journals Water and solute permeabilities of medullary thick ascending limb apical and basolateral membranes

1998 ◽  
Vol 274 (3) ◽  
pp. F453-F462 ◽  
Author(s):  
Rickey Rivers ◽  
Anne Blanchard ◽  
Dominique Eladari ◽  
Francois Leviel ◽  
Michel Paillard ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Basolateral Membrane ◽  
Thick Ascending Limb ◽  
Membrane Structures ◽  
Membrane Unit ◽  
Small Surface ◽  
Basolateral Membranes ◽  
Medullary Thick Ascending Limb ◽  
Osmotic Water

The medullary thick ascending limb (MTAL) reabsorbs solute without water and concentrates [Formula: see text] in the interstitium without a favorable pH gradient, activities which require low water and NH3 permeabilities. The contributions of different apical and basolateral membrane structures to these low permeabilities are unclear. We isolated highly purified apical and basolateral MTAL plasma membranes and measured, by stopped-flow fluorometry, their permeabilities to water, urea, glycerol, protons, and NH3. Osmotic water permeability at 20°C averaged 9.4 ± 0.8 × 10−4 cm/s for apical and 11.9 ± 0.5 × 10−4cm/s for basolateral membranes. NH3 permeabilities at 20°C averaged 0.0023 ± 0.00035 and 0.0035 ± 0.00080 cm/s for apical and basolateral membranes, respectively. These values are consistent with those obtained in isolated perfused tubules and can account for known aspects of MTAL function in vivo. Because the apical and basolateral membrane unit permeabilities are similar, the ability of the apical membrane to function as the site of barrier function arises from its very small surface area when compared with the highly redundant basolateral membrane.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

On the differentiation of prospective ectoderm to a ciliated cell pattern in embryos of Ambystoma mexicanum

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 23-32
Author(s):  
Ulf Landström
Keyword(s):  
Ciliated Cell ◽  
Inhibitory Effect ◽  
Ambystoma Mexicanum ◽  
Epidermal Differentiation ◽  
Contact Transformation ◽  
Ciliated Cells ◽  
Experimental Conditions ◽  
Cell Pattern

The differentiation of the ectoderm in Ambystoma mexicanum (Harrison stage 26–27) was examined under in vivo and in vitro conditions by scanning electron microscopy under different experimental conditions. About one out of three flank epidermal cells was found to be ciliated in the undisturbed or control embryos. The shape of ciliated cells in the explants from the animal region was only slightly affected. In no case was it possible to find two adjacent ciliated cells, implying that these cells prevent the appearance of cilia in the cells in direct contact. Transformation to ciliated cells is suppressed by hypertonicity but favoured in a hypotonic medium. The differentiation of epidermis is also dependent upon the synthesis of RNA and some kind of sulphated glucosaminoglycan, corroborated by the inhibitory effect of actinomycin and selenate. The differences between the test series and the controls are discussed with regard to factors controlling embryonic epidermal differentiation.

scholarly journals Ionic conductance pathways in the mouse medullary thick ascending limb of Henle. The paracellular pathway and electrogenic Cl- absorption.

1986 ◽  
Vol 87 (4) ◽  
pp. 567-590 ◽  
Author(s):  
S C Hebert ◽  
T E Andreoli
Keyword(s):  
Apical Membrane ◽  
Electrical Conductance ◽  
Transport Processes ◽  
Diffusion Resistance ◽  
Osmotic Gradient ◽  
Thick Ascending Limb ◽  
Nacl Absorption ◽  
Medullary Thick Ascending Limb ◽  
Paired Measurement

Net Cl- absorption in the mouse medullary thick ascending limb of Henle (mTALH) involves a furosemide-sensitive Na+:K+:2 Cl- apical membrane symport mechanism for salt entry into cells, which occurs in parallel with a Ba++-sensitive apical K+ conductance. The present studies, using the in vitro microperfused mouse mTALH, assessed the concentration dependence of blockade of this apical membrane K+-conductive pathway by Ba++ to provide estimates of the magnitudes of the transcellular (Gc) and paracellular (Gs) electrical conductances (millisiemens per square centimeter). These studies also evaluated the effects of luminal hypertonicity produced by urea on the paracellular electrical conductance, the electrical Na+/Cl- permselectivity ratio, and the morphology of in vitro mTALH segments exposed to peritubular antidiuretic hormone (ADH). Increasing luminal Ba++ concentrations, in the absence of luminal K+, produced a progressive reduction in the transcellular conductance that was maximal at 20 mM Ba++. The Ba++-sensitive transcellular conductance in the presence of ADH was 61.8 +/- 1.7 mS/cm2, or approximately 65% of the total transepithelial conductance. In phenomenological terms, the luminal Ba++-dependent blockade of the transcellular conductance exhibited negative cooperativity. The transepithelial osmotic gradient produced by luminal urea produced blebs on apical surfaces, a striking increase in shunt conductance, and a decrease in the shunt Na+/Cl- permselectivity (PNa/PCl), which approached that of free solution. The transepithelial conductance obtained with luminal 800 mM urea, 20 mM Ba++, and 0 K+ was 950 +/- 150 mS/cm2 and provided an estimate of the maximal diffusion resistance of intercellular spaces, exclusive of junctional complexes. The calculated range for junctional dilution voltages owing to interspace salt accumulation during ADH-dependent net NaCl absorption was 0.7-1.1 mV. Since the Ve accompanying ADH-dependent net NaCl absorption is 10 mV, lumen positive, virtually all of the spontaneous transepithelial voltage in the mouse mTALH is due to transcellular transport processes. Finally, we developed a series of expressions in which the ratio of net Cl- absorption to paracellular Na+ absorption could be expressed in terms of a series of electrical variables. Specifically, an analysis of paired measurement of PNa/PCl and Gs was in agreement with an electroneutral Na+:K+:2 Cl- apical entry step. Thus, for net NaCl absorption, approximately 50% of Na+ was absorbed via a paracellular route.

Lack of potassium effect on Na-Cl cotransport in the medullary thick ascending limb

1985 ◽  
Vol 249 (1) ◽  
pp. F34-F39 ◽  
Author(s):  
M. Alvo ◽  
J. Calamia ◽  
J. Eveloff
Keyword(s):  
Inhibitory Effect ◽  
Thick Ascending Limb ◽  
Experimental Conditions ◽  
Chloride Uptake ◽  
Medullary Thick Ascending Limb ◽  
Significant Inhibitory Effect ◽  
Cotransport System ◽  
Nacl Cotransport ◽  
Na Uptake ◽  
External K

The effect of potassium on sodium chloride uptake into rabbit renal medullary thick ascending limb of Henle's loop (mTALH) cells was studied to assess whether K participates in the Na-Cl cotransport system. Na uptake into the mTALH cells was inhibited 70% at 3 min by 1 mM furosemide. The total and furosemide-sensitive Na uptake was stimulated by Cl. Additionally, Cl uptake into the mTALH cells was stimulated by Na gradients and inhibited 42% at 3 min by 1 mM furosemide. Na uptake was studied in the presence of 0,5, or 140 mM external K gradients. Na uptake was similar in the absence and presence of K. Additionally, furosemide inhibited Na uptake as effectively in the absence or presence of K. Similar studies were conducted to study the effects of Na on 86Rb uptake. Na did not stimulate 86Rb uptake. The uptake of 86Rb was similar in the presence of 0,5, or 140 mM Na gradients. Furosemide had no significant inhibitory effect on 86Rb uptake. Barium (5 mM), an inhibitor of K conductance pathways, inhibited total 86Rb uptake by 19%. In the presence of 5 mM BaCl2, Na still did not have a stimulatory effect on 86Rb uptake. The results confirm the existence of a Na-Cl cotransport system in mTALH cells, but a direct effect of K on the NaCl cotransport system could not be demonstrated under the experimental conditions we used.

scholarly journals Regulation of the renal Na:K pump: role of progesterone.

1993 ◽  
Vol 3 (8) ◽  
pp. 1488-1495
Author(s):  
S K Mujais ◽  
N A Nora ◽  
Y Chen
Keyword(s):  
Inhibitory Effect ◽  
Proximal Convoluted Tubule ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Medullary Thick Ascending Limb ◽  
Progesterone Treatment ◽  
Sprague Dawley Rats ◽  
High K ◽  
Pump Activity ◽  
Intact Rats

In male Sprague-Dawley rats, the effects of exogenous high physiologic levels of progesterone simulating those observed in pregnancy (5 mg/day) on Na:K pump activity (picomoles per millimeter per hour) in microdissected nephron segments were evaluated. In adrenal-intact rats, progesterone led to a generalized decrease in Na:K pump activity in proximal convoluted tubule from 2,524 +/- 61 to 741 +/- 41 (71% reduction; P < 0.01), medullary thick ascending limb (MAL) from 4,793 +/- 217 to 2,000 +/- 133 (59% reduction; P < 0.01), and cortical collecting tubule (CCT) from 1,141 +/- 69 to 591 +/- 133 (49% reduction; P < 0.01). This effect was similar in magnitude to the decline observed with adrenalectomy alone. In adrenalectomized rats, progesterone had no further inhibitory effect on the pump in MAL (2,172 +/- 66 versus 2,312 +/- 71) or CCT (493 +/- 58 versus 530 +/- 31) but led to a modest decline in Na:K pump activity in the proximal convoluted tubule (from 1,136 +/- 88 to 528 +/- 31; P < 0.01). In adrenal-intact rats, a high K diet for 7 days led to an increase in CCT Na:K pump activity from 1,141 +/- 69 on a normal potassium diet to 2,224 +/- 33 pmol/mm per h (P < 0.001). Progesterone treatment reduced basal Na:K pump activity in CCT, and concurrent progesterone treatment blunted the stimulatory effect of K adaptation on the pump (973 +/- 68 pmol/mm per h; P < 0.001 versus untreated).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ADH on chloride reabsorption in the loop of Henle of the Brattleboro rat

1985 ◽  
Vol 249 (5) ◽  
pp. F698-F703 ◽  
Author(s):  
J. Work ◽  
J. H. Galla ◽  
B. B. Booker ◽  
J. A. Schafer ◽  
R. G. Luke
Keyword(s):  
Distal Tubule ◽  
Thick Ascending Limb ◽  
Brattleboro Rat ◽  
In Vitro Perfusion ◽  
Chloride Flux ◽  
Medullary Thick Ascending Limb ◽  
Transepithelial Voltage ◽  
Tubule Fluid

Both in vivo superficial loop segment microperfusion and in vitro perfusion of isolated medullary thick ascending limb segments were used to assess the effect of vasopressin on loop of Henle chloride absorption in the Brattleboro rat. Superficial loop segments were perfused between the latest proximal and earliest distal tubule in vivo at 19.2 +/- 0.4 nl/min (mean +/- SE) with an artificial tubule fluid. Under control conditions, absolute chloride reabsorption was 1,596 +/- 61 pmol/min and increased to 1,876 +/- 102 after intravenous infusion of vasopressin (P less than 0.005). Distal tubule fluid chloride concentration decreased 4.6 +/- 1.5 meq/liter (P less than 0.05), and fractional chloride reabsorption increased 4.8 +/- 2.0% (P less than 0.05). For in vitro perfusion, medullary thick ascending limb segments were bathed and perfused (9-15 nl/min) with phosphate-buffered solutions at 38 degrees C. Under control conditions, transepithelial voltage was +2.4 +/- 0.3 mV, lumen positive, and the net chloride flux was 147 +/- 24 pmol X min-1 X mm-1 in the absorptive direction. Addition of vasopressin to the bathing solution increased net chloride reabsorption to 342 +/- 56 pmol X min-1 X mm-1 (P less than 0.02) and transepithelial voltage to 3.0 +/- 0.3 mV (P less than 0.002). An additional group of tubules was examined under identical conditions; however, vasopressin was removed from the bathing medium during a subsequent recovery period. In these experiments, net chloride flux and transepithelial voltage significantly increased compared with the control period and returned to control values upon removal of vasopressin from the bath.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regulation of angiotensin II and losartan binding sites in glomeruli and mesangial cells

1994 ◽  
Vol 266 (3) ◽  
pp. F384-F393 ◽  
Author(s):  
D. Chansel ◽  
T. Bizet ◽  
S. Vandermeersch ◽  
P. Pham ◽  
B. Levy ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Binding Sites ◽  
Mesangial Cells ◽  
Present Report ◽  
Mrna Levels ◽  
Ang Ii ◽  
Experimental Conditions ◽  
Human Mesangial Cells

The aim of the present report was to examine the effect of several agents on angiotensin II (ANG II) and losartan receptors using 125I-[Sar1,Ala8]ANG II and [3H]losartan as radiolabeled ligand, respectively. ANG II receptors were downregulated in glomeruli from rats infused with ANG II during 3 wk or rats receiving losartan orally during 1 wk. The number of sites (Bmax) was reduced, but the dissociation constant (Kd) value was unchanged. Losartan receptors were downregulated in glomeruli from rats receiving losartan, but remained unchanged in glomeruli from rats infused with ANG II. Since in vivo administration of losartan results in increase of plasma ANG II and formation of metabolites, in vitro studies using human mesangial cells were performed to better analyze the present findings. Treatment of mesangial cells during 4 days by ANG II, losartan, or its metabolite, EXP-3174, also produced downregulation of 125I-[Sar1,Ala8]ANG II binding sites with a decreased Bmax and unchanged Kd value. Only treatment of mesangial cells by ANG II or EXP-3174 produced downregulation of [3H]losartan binding sites. In contrast, exposure of these cells to losartan resulted in upregulation of [3H]losartan binding sites. Under all conditions, only Bmax was modified. Whereas internalization of [3H]losartan in mesangial cells was negligible under all experimental conditions, there was an increase of the percentage of internalized 125I-[Sar1,Ala8]ANG II after exposure of the cells to ANG II or AT1 antagonists. No change was observed in mesangial cell AT1 receptor mRNA levels. This study demonstrates that 1) AT1 mRNA is expressed in human mesangial cells; 2) the characteristics of 125I-[Sar1,Ala8]ANG II and [3H]losartan binding sites in rat glomeruli and human mesangial cells are different, with Kd and Bmax values greater in both preparations when [3H]losartan was utilized; 3) both types of binding sites obey different regulations, and the effects of losartan in vivo are due in part to the associated increase in plasma ANG II levels and the transformation of the drug into its metabolite, EXP-3174; 4) downregulation of AT1 receptors does not depend on changes in mRNA expression but is associated with increased relative internalization.

Ischemia-reperfusion induces G-CSF gene expression by renal medullary thick ascending limb cells in vivo and in vitro

2004 ◽  
Vol 286 (6) ◽  
pp. F1193-F1201 ◽  
Author(s):  
Ying Zhang ◽  
Vanessa K. Woodward ◽  
John M. Shelton ◽  
James A. Richardson ◽  
Xin J. Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Thick Ascending Limb ◽  
Rnase Protection ◽  
Medullary Thick Ascending Limb ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

Ischemic acute renal failure involves not only the kidney but also extrarenal organs such as the bone marrow that produces inflammatory cells. By ELISA and RNase protection assays, we now show that renal ischemia-reperfusion increases serum concentrations of granulocyte macrophage colony-stimulating factor (G-CSF) protein and increases both G-CSF mRNA and protein in the ischemic kidney. In situ hybridization localized the increased G-CSF mRNA to tubule cells, including medullary thick ascending limb cells (mTAL), in the outer medulla. We also show that mTAL produce G-CSF protein and increase G-CSF mRNA after stimulation by reactive oxygen species in vitro. The production of G-CSF by the kidney after ischemia-reperfusion provides a means of communication from the injured kidney to the bone marrow. This supports the known inflammatory response to ischemia.

scholarly journals Angiotensin II Signaling Promotes Follicle Growth and Dominance in Cattle

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4957-4965 ◽  
Author(s):  
Rogério Ferreira ◽  
Bernardo Gasperin ◽  
Monique Rovani ◽  
Joabel Santos ◽  
Marcos Barreta ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Granulosa Cell ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Follicular Growth ◽  
Dominant Follicle ◽  
Follicle Growth ◽  
Angiotensin Ii Signaling

It is generally understood that angiotensin II (AngII) promotes follicle atresia in rats, although recent data suggested that this may not be true in cattle. In this study, we aimed to determine in vivo whether AngII alters follicle development in cattle, using intrafollicular injection of AngII or antagonist into the growing dominant follicle or the second largest subordinate follicle. Injection of saralasin, an AngII antagonist, into the growing dominant follicle inhibited follicular growth, and this inhibitory effect was overcome by systemic FSH supplementation. Injection of AngII into the dominant follicle did not affect follicular growth, whereas injection of AngII into the second largest follicle prevented the expected atresia of this subordinate follicle, and the treated follicle grew at the same rate as the dominant follicle for the next 24 h. Inhibition of AngII action in the dominant follicle decreased estradiol concentrations in follicular fluid and the abundance of mRNA encoding aromatase, 3β-hydroxysteroid dehydrogenase, LH receptor, and cyclinD2 in granulosa cells, with minimal effects on theca cells. The effect of AngII on aromatase mRNA levels was confirmed using an in vitro granulosa cell culture system. In conclusion, these data suggest that AngII signaling promotes follicle growth in cattle and does so by regulating genes involved in estradiol secretion and granulosa cell proliferation and differentiation.

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