Regulation of luminal alkalinization and acidification in the cortical collecting duct by angiotensin II

1995 ◽  
Vol 269 (5) ◽  
pp. F730-F738 ◽  
Author(s):  
I. D. Weiner ◽  
A. R. New ◽  
A. E. Milton ◽  
C. C. Tisher
Keyword(s):  
Angiotensin Ii ◽  
B Cell ◽  
Collecting Duct ◽  
At1 Receptor ◽  
Rate Of Change ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Stop Flow

Angiotensin II (ANG II) regulates whole kidney ion transport, yet its effects in the collecting duct are unknown. The purpose of these studies was to determine whether ANG II regulates luminal alkalinization and acidification in the rabbit cortical collecting duct (CCD). The rate of luminal alkalinization or acidification was measured as the rate of change of luminal fluid pH under stop-flow conditions using in vitro microperfused CCD segments. Outer CCD alkalinized the luminal fluid, consistent with net HCO3- secretion. Addition of ANG II, 10(-7) M, to the peritubular solution for 30 min significantly stimulated luminal alkalinization. The stimulatory effect of ANG II was not due to time-dependent effects and was blocked by peritubular addition of the ANG II type 1 (AT1) receptor antagonist, losartan, at 10(-6) M. Losartan, 10(-6) M, when added to the peritubular solution, did not alter the rate of luminal alkalinization independent of ANG II. In contrast, peritubular ANG II, 10(-7) M, did not alter inner CCD luminal acidification. Addition of ANG II to the peritubular solution at the lower concentration of 10(-10) M did not alter the rates of luminal alkalinization and acidification in the outer and inner CCD, respectively. Peritubular ANG II, 10(-7) M, but not vehicle, stimulated B cell apical HCO3- secretion occurring in response to peritubular Cl- removal. These studies demonstrate that ANG II acts through a basolateral AT1 receptor to stimulate outer CCD luminal alkalinization via, at least in part, B cell stimulation.

scholarly journals Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

2010 ◽  
Vol 299 (3) ◽  
pp. F577-F584 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Sandra Summer ◽  
Sandor Falk ◽  
Robert W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Urine Concentration ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Vitro Effect

The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 ± 0.1 in dDAVP+losartan (LSDL) vs. 1.1 ± 0.1 ml·100 g−1·day−1 in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 ± 0.5 in LSDL vs. 6.8 ± 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 ± 0.2 vs. 1.8 ± 0.2 ml·100 g−1·day−1, P < 0.05) in association with decreased urine osmolality (2,600 ± 83 vs. 3,256 ± 110 mosmol/kgH2O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 ± 6 vs. 176 ± 10% in LSD, P < 0.01), p-AQP2 (177 ± 13 vs. 214 ± 12% in LSD, P < 0.05), and AQP3 (134 ± 14 vs. 177 ± 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the α1- and γ-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.

scholarly journals Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron.

1997 ◽  
Vol 8 (11) ◽  
pp. 1658-1667 ◽  
Author(s):  
N Bouby ◽  
A Hus-Citharel ◽  
J Marchetti ◽  
L Bankir ◽  
P Corvol ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Nephron Segments

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.

scholarly journals The Angiotensin II Type 1 Receptor-Associated Protein Attenuates Angiotensin II-Mediated Inhibition of the Renal Outer Medullary Potassium Channel in Collecting Duct Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Juliano Zequini Polidoro ◽  
Nancy Amaral Rebouças ◽  
Adriana Castello Costa Girardi
Keyword(s):  
Angiotensin Ii ◽  
Cell Surface ◽  
Collecting Duct ◽  
Cell Surface Expression ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

Adjustments in renal K+ excretion constitute a central mechanism for K+ homeostasis. The renal outer medullary potassium (ROMK) channel accounts for the major K+ secretory route in collecting ducts during basal conditions. Activation of the angiotensin II (Ang II) type 1 receptor (AT1R) by Ang II is known to inhibit ROMK activity under the setting of K+ dietary restriction, underscoring the role of the AT1R in K+ conservation. The present study aimed to investigate whether an AT1R binding partner, the AT1R-associated protein (ATRAP), impacts Ang II-mediated ROMK regulation in collecting duct cells and, if so, to gain insight into the potential underlying mechanisms. To this end, we overexpressed either ATRAP or β-galactosidase (LacZ; used as a control), in M-1 cells, a model line of cortical collecting duct cells. We then assessed ROMK channel activity by employing a novel fluorescence-based microplate assay. Experiments were performed in the presence of 10−10 M Ang II or vehicle for 40 min. We observed that Ang II-induced a significant inhibition of ROMK in LacZ, but not in ATRAP-overexpressed M-1 cells. Inhibition of ROMK-mediated K+ secretion by Ang II was accompanied by lower ROMK cell surface expression. Conversely, Ang II did not affect the ROMK-cell surface abundance in M-1 cells transfected with ATRAP. Additionally, diminished response to Ang II in M-1 cells overexpressing ATRAP was accompanied by decreased c-Src phosphorylation at the tyrosine 416. Unexpectedly, reduced phospho-c-Src levels were also found in M-1 cells, overexpressing ATRAP treated with vehicle, suggesting that ATRAP can also downregulate this kinase independently of Ang II-AT1R activation. Collectively, our data support that ATRAP attenuates inhibition of ROMK by Ang II in collecting duct cells, presumably by reducing c-Src activation and blocking ROMK internalization. The potential role of ATRAP in K+ homeostasis and/or disorders awaits further investigation.

scholarly journals Site-1 Protease-Derived Soluble (Pro)Renin Receptor Contributes to Angiotensin II–Induced Hypertension in Mice

Hypertension ◽  
2020 ◽  
Author(s):  
Ye Feng ◽  
Kexin Peng ◽  
Renfei Luo ◽  
Fei Wang ◽  
Tianxin Yang
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Collecting Duct ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Short Circuit Current ◽  
Duct Cell ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Induced Hypertension

Activation of PRR ([pro]renin receptor) contributes to enhancement of intrarenal RAS and renal medullary α-ENaC and thus elevated blood pressure during Ang II (angiotensin II) infusion. The goal of the present study was to test whether such action of PRR was mediated by sPRR (soluble PRR), generated by S1P (site-1 protease), a newly identified PRR cleavage protease. F1 B6129SF1/J mice were infused for 6 days with control or Ang II at 300 ng/kg per day alone or in combination with S1P inhibitor PF-429242 (PF), and blood pressure was monitored by radiotelemetry. S1P inhibition significantly attenuated Ang II–induced hypertension accompanied with suppressed urinary and renal medullary renin levels and expression of renal medullary but not renal cortical α-ENaC expression. The effects of S1P inhibition were all reversed by supplement with histidine-tagged sPRR termed as sPRR-His. Ussing chamber technique was performed to determine amiloride-sensitive short-circuit current, an index of ENaC activity in confluent mouse cortical collecting duct cell line cells exposed for 24 hours to Ang II, Ang II + PF, or Ang II + PF + sPRR-His. Ang II–induced ENaC activity was blocked by PF, which was reversed by sPRR-His. Together, these results support that S1P-derived sPRR mediates Ang II–induced hypertension through enhancement of intrarenal renin level and activation of ENaC.

Glomerular effects of angiotensin II require intrarenal factors

1990 ◽  
Vol 258 (3) ◽  
pp. F717-F721 ◽  
Author(s):  
T. B. Wiegmann ◽  
M. L. MacDougall ◽  
V. J. Savin
Keyword(s):  
Angiotensin Ii ◽  
Rate Of Change ◽  
Ang Ii ◽  
Membrane Area ◽  
Isolated Glomeruli ◽  
Systemic Factors ◽  
Glomerular Ultrafiltration

Glomerular ultrafiltration coefficient (Kf) of glomeruli isolated from kidneys of normovolemic rats decreases following infusion of angiotensin II (ANG II). Kf from isolated glomeruli after ANG II infusion in vivo and from isolated perfused kidneys following infusion of ANG II in vitro was measured to determine whether the decrease required the presence of systemic factors. Filtration was induced in vitro and the maximum rate of change in glomerular volume was used to calculate Kf. Glomerular capillary hydraulic conductivity (Lp) was calculated from Lp = Kf/A where the basement membrane area A was calculated as 3 X pi X D2. ANG II infusion in vivo in rats diminished Lp from 3.19 +/- 0.19 to 1.96 +/- 0.13 and to 1.82 +/- 0.11 microliters.min-1.mmHg-1.cm-2, respectively. ANG II infusion into isolated kidneys caused a similar decrease in Lp (3.55 +/- 0.11 to 2.37 +/- 0.07). ANG II infusion either in vivo or during isolated kidney perfusion decreases Kf and Lp. ANG II effects do not require the presence of extrarenal factors but depend on perfusion in situ since incubation of isolated glomeruli with ANG II did not alter Kf.

Angiotensin II type 1 receptor modulation of neuronal K+ and Ca2+ currents: intracellular mechanisms

1996 ◽  
Vol 271 (1) ◽  
pp. C154-C163 ◽  
Author(s):  
C. Sumners ◽  
M. Zhu ◽  
C. H. Gelband ◽  
P. Posner
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Ang Ii ◽  
Receptor Modulation ◽  
Kinase C ◽  
Intracellular Messengers ◽  
Voltage Dependent ◽  
K Current ◽  
Stimulation Of

Angiotensin II (ANG II) elicits an ANG II type 1 (AT1) receptor-mediated decrease in voltage-dependent K+ current (Ik) and an incrase in voltage-dependent Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem. Modulation of these currents by ANG II involves intracellular messengers that result from an AT1 receptor-mediated stimulation of phosphoinositide hydrolysis. For example, the effects of ANG II on IK and ICa were abolished by phospholipase C antagonists. The reduction in IK produced by ANG II was attenuated by either protein kinase C (PKC) antagonists or by chelation of intracellular Ca2+. By contrast, PKC antagonism abolished the stimulatory effect of ANG II on ICa. Superfusion of the PKC activator phorbol 12-myristate 13-acetate produced effects on IK and ICa similar to those observed after ANG II. Furthermore, intracellular application of inositol 1,4,5-trisphosphate (IP3) elicited a significant reduction in IK. This suggests that the AT1 receptor-mediated changes in neuronal K+ and Ca2+ currents involve PKC (both IK and ICa) and IP3 and/or intracellular Ca2+ (IK).

scholarly journals Angiotensin II type 2 receptor regulates ROMK-like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation

2014 ◽  
Vol 307 (7) ◽  
pp. F833-F843 ◽  
Author(s):  
Yuan Wei ◽  
Yi Liao ◽  
Beth Zavilowitz ◽  
Jin Ren ◽  
Wen Liu ◽  
...  
Keyword(s):  
Collecting Duct ◽  
No Synthase ◽  
K Channel ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Channel Activity ◽  
High K ◽  
Pka Pathway

The kidney adjusts K+ excretion to match intake in part by regulation of the activity of apical K+ secretory channels, including renal outer medullary K+ (ROMK)-like K+ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K+ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K+ (HK)-fed but not normal K+ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K+-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway.

scholarly journals Angiotensin II stimulates epithelial sodium channels in the cortical collecting duct of the rat kidney

2012 ◽  
Vol 302 (6) ◽  
pp. F679-F687 ◽  
Author(s):  
Peng Sun ◽  
Peng Yue ◽  
Wen-Hui Wang
Keyword(s):  
Angiotensin Ii ◽  
Single Channel ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
Whole Cell ◽  
Na Currents

We examined the effect of angiotensin II (ANG II) on epithelial Na+channel (ENaC) in the rat cortical collecting duct (CCD) with single-channel and the perforated whole cell patch-clamp recording. Application of 50 nM ANG II increased ENaC activity, defined by NPo(a product of channel numbers and open probability), and the amiloride-sensitive whole cell Na currents by twofold. The stimulatory effect of ANG II on ENaC was absent in the presence of losartan, suggesting that the effect of ANG II on ENaC was mediated by ANG II type 1 receptor. Moreover, depletion of intracellular Ca2+with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA)-AM failed to abolish the stimulatory effect of ANG II on ENaC but inhibiting protein kinase C (PKC) abolished the effect of ANG II, suggesting that the effect of ANG II was the result of stimulating Ca2+-independent PKC. This notion was also suggested by the experiments in which stimulation of PKC with phorbol ester derivative mimicked the effect of ANG II and increased amiloride-sensitive Na currents in the principal cell, an effect that was not abolished by treatment of the CCD with BAPTA-AM. Also, inhibition of NADPH oxidase (NOX) with diphenyleneiodonium chloride abolished the stimulatory effect of ANG II on ENaC and application of superoxide donors, pyrogallol or xanthine and xanthine oxidase, significantly increased ENaC activity. Moreover, addition of ANG II or H2O2diminished the arachidonic acid (AA)-induced inhibition of ENaC in the CCD. We conclude that ANG II stimulates ENaC in the CCD through a Ca2+-independent PKC pathway that activates NOX thereby increasing superoxide generation. The stimulatory effect of ANG II on ENaC may be partially the result of blocking AA-induced inhibition of ENaC.

scholarly journals High intraluminal pressure via H2O2 upregulates arteriolar constrictions to angiotensin II by increasing the functional availability of AT1 receptors

2008 ◽  
Vol 295 (2) ◽  
pp. H835-H841 ◽  
Author(s):  
Zsolt Bagi ◽  
Nora Erdei ◽  
Akos Koller
Keyword(s):  
High Pressure ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Intraluminal Pressure ◽  
Ang Ii ◽  
At1 Receptors ◽  
Angiotensin System ◽  
Dose Dependent

Previously, we found that high intraluminal pressure leads to production of reactive oxygen species (ROS) and also upregulates several components of the renin-angiotensin system in the wall of small arteries. We hypothesized that acute exposure of arterioles to high intraluminal pressure in vitro via increasing ROS production enhances the functional availability of type 1 angiotensin II (Ang II) receptors (AT1 receptors), resulting in sustained constrictions. In arterioles (∼180 μm) isolated from rat skeletal muscle, Ang II elicited dose-dependent constrictions, which decreased significantly by the second application [maximum (max.): from 59% ± 4% to 26% ± 5% at 10−8 M; P < 0.05] in the presence of 80 mmHg of intraluminal pressure. In contrast, if the arterioles were exposed to high intraluminal pressure (160 mmHg for 30 min), Ang II-induced constrictions remained substantial on the second application (max.: 51% ± 3% at 10−8 M). In the presence of Tiron and polyethylene glycol (PEG)-catalase, known to reduce the level of superoxide anion and hydrogen peroxide (H2O2), second applications of Ang II evoked similarly reduced constrictions, even after high-pressure exposure (29% ± 4% at 10−8 M). Furthermore, when arterioles were exposed to H2O2 (for 30 min, 10−7 M, at normal 80 mmHg pressure), Ang II-induced constrictions remained substantial on second applications (59% ± 5% at 10−8 M). These findings suggest that high pressure, likely via inducing H2O2 production, increases the functional availability of AT1 receptors and thus enhances Ang II-induced arteriolar constrictions. We propose that in hypertension–regardless of etiology–high intraluminal pressure, via oxidative stress, enhances the functional availability of AT1 receptors augmenting Ang II-induced constrictions.

scholarly journals Role of basic amino acids of the human angiotensin type 1 receptor in the binding of the non-peptide antagonist candesartan

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S32-S36 ◽  
Author(s):  
Georges Vauquelin ◽  
Frederik LP Fierens ◽  
Zsuzsanna Gáborik ◽  
Tam Le Minh ◽  
Jean-Paul De Backer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Angiotensin Ii ◽  
Ligand Binding ◽  
At1 Receptor ◽  
Ang Ii ◽  
Binding Properties ◽  
Basic Amino Acids ◽  
Peptide Antagonist ◽  
The Impact

To explain the insurmountable/long-lasting binding of biphenyltetrazole-containing AT1-receptor antagonists such as candesartan, to the human angiotensin II type 1-receptor, a model is proposed in which the basic amino acids Lys199 and Arg 167 of the receptor interact respectively with the carboxylate and the tetrazole group of the antagonists. To validate this model, we have investigated the impact of substitution of Lys199 by Ala or Gln and of Arg167 by Ala on the binding properties of [3H]candesartan and on competition binding by candesartan, EXP3174, irbesartan, losartan, angiotensin II (Ang II) and [Sar1-Ile8]angiotensin. Our results indicate that both amino acids play an important role in the AT1-receptor ligand binding. Whereas the negative charge of Lys 199 is involved in an ionic bond with the end-standing carboxylate group of the peptide ligands, its polarity also contributes to the non-peptide antagonist binding. Substitution of Arg167 by Ala completely abolished [3H]Ang II, as well as [3H] candesartan, binding. Whereas these results are in line with the proposed model, it cannot be excluded that both amino acid residues are important for the structural integrity of the AT1-receptor with respect to its ligand binding properties.

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