Effects of angiotensin II on the CO2 dependence of HCO3− reabsorption by the rabbit S2 renal proximal tubule

2006 ◽  
Vol 290 (3) ◽  
pp. F666-F673 ◽  
Author(s):  
Yuehan Zhou ◽  
Patrice Bouyer ◽  
Walter F. Boron
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Signal Transduction Pathways ◽  
Low Doses ◽  
Ang Ii ◽  
Reabsorption Rate ◽  
Fractional Inhibition

Previous authors showed that, at low doses, both basolateral and luminal ANG II increase the proximal tubule's HCO3− reabsorption rate ( JHCO3). Using out-of-equilibrium CO2/HCO3− solutions, we demonstrated that basolateral CO2 increases JHCO3. Here, we examine interactions between ANG II and CO2 in isolated, perfused rabbit S2 segments. We first used equilibrated 5% CO2/22 mM HCO3−/pH 7.40 in bath and lumen. At 10−11 M, basolateral (BL) ANG II increased JHCO3 by 41%, and luminal ANG II increased JHCO3 by 35%. At 10−9 M, basolateral ANG II decreased JHCO3 by 43%, whereas luminal ANG II was without effect. Second, we varied [CO2]BL from 0 to 20% at fixed [HCO3−]BL and pHBL. Fractional stimulation produced by BL 10−11 M ANG II falls when [CO2]BL exceeds 5%. Fractional inhibition produced by BL 10−9 M ANG II tends to rise when [CO2]BL exceeds 5%. Regarding luminal ANG II, fractional stimulation produced by 10−11 M ANG II fell monotonically as [CO2]BL rose from 0 to 20%. Fractional inhibition produced by 10−9 M ANG II rose monotonically with increasing [CO2]BL. Viewed differently, ANG II at 10−11 M tended to reduce stimulation by CO2, and at 10−9 M, produced an even greater reduction. In conclusion, the mutual effects of 1) ANG II on the JHCO3 response to basolateral CO2 and 2) basolateral CO2 on the JHCO3 responses to ANG II suggest that the signal-transduction pathways for ANG II and basolateral CO2 intersect or merge.

Lipid signal transduction pathways in angiotensin II type 1 receptor-transfected fibroblasts

1995 ◽  
Vol 269 (2) ◽  
pp. C435-C442 ◽  
Author(s):  
Y. Wen ◽  
M. C. Cabot ◽  
E. Clauser ◽  
S. L. Bursten ◽  
J. L. Nadler
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Chinese Hamster ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Ang Ii ◽  
Vascular Type ◽  
Lipid Signal ◽  
Fibroblast Line

A stable Chinese hamster ovary fibroblast line expressing the rat vascular type 1a angiotensin II (ANG II) receptor was used to study the lipid-derived signal transduction pathways elicited by type 1a ANG II receptor activation. ANG II caused a biphasic and dose-dependent increase in diacylglycerol (DAG) accumulation with an initial peak at 15 s (181 +/- 11% of control, P < 0.02) and a second sustained peak at 5-10 min (214 +/- 10% of control, P < 0.02). The late DAG peak was derived from phosphatidylcholine (PC), and the formation was blocked by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. ANG II also increased phosphatidic acid (PA) production nearly fourfold by 7.5 min. In the presence of ethanol, ANG II markedly increased phosphatidylethanol (PEt) formation, indicating activation of phospholipase D (PLD). ANG II was shown to increase the mass of three separate PA species, one of which apparently originated from DAG kinase action on PC-phospholipase C (PLC)-produced DAG, providing evidence for PC-PLC activity. ANG II also formed a third PA species, which originated neither from PLD nor from DAG kinase. These results demonstrate that multiple lipid signals propagated via collateral stimulation of PLC and PLD are generated by specific activation of the vascular type 1a ANG II receptor.

scholarly journals Dietary fructose enhances angiotensin II-stimulated Na+ transport via activation of PKC-α in renal proximal tubules

2020 ◽  
Vol 318 (6) ◽  
pp. F1513-F1519
Author(s):  
Nianxin Yang ◽  
Nancy J. Hong ◽  
Jeffrey L. Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Tap Water ◽  
Renal Proximal Tubule ◽  
Proximal Tubules ◽  
Control Group ◽  
Ang Ii ◽  
Dietary Fructose ◽  
Intracellular Ca ◽  
Pkc Β

Angiotensin II (ANG II) stimulates proximal nephron transport via activation of classical protein kinase C (PKC) isoforms. Acute fructose treatment stimulates PKC and dietary fructose enhances ANG II’s ability to stimulate Na+ transport, but the mechanisms are unclear. We hypothesized that dietary fructose enhances ANG II’s ability to stimulate renal proximal tubule Na+ reabsorption by augmenting PKC-α activation and increases in intracellular Ca2+. We measured total and isoform-specific PKC activity, basal and ANG II-stimulated oxygen consumption, a surrogate of Na+ reabsorption, and intracellular Ca2+ in proximal tubules from rats given either 20% fructose in their drinking water (fructose group) or tap water (control group). Total PKC activity was measured by ELISA. PKC-α, PKC-β, and PKC-γ activities were assessed by measuring particulate-to-soluble ratios. Intracelluar Ca2+ was measured using fura 2. ANG II stimulated total PKC activity by 53 ± 15% in the fructose group but not in the control group (−15 ± 11%, P < 0.002). ANG II stimulated PKC-α by 0.134 ± 0.026 but not in the control group (−0.002 ± 0.020, P < 0.002). ANG II increased PKC-γ activity by 0.008 ± 0.003 in the fructose group but not in the control group ( P < 0.046). ANG II did not stimulate PKC-β in either group. ANG II increased Na+ transport by 454 ± 87 nmol·min−1·mg protein−1 in fructose group, and the PKC-α/β inhibitor Gö6976 blocked this increase (−96 ± 205 nmol·min−1·mg protein−1, P < 0.045). ANG II increased intracellular Ca2+ by 148 ± 53 nM in the fructose group but only by 43 ± 10 nM in the control group ( P < 0.035). The intracellular Ca2+ chelator BAPTA blocked the ANG II-induced increase in Na+ transport in the fructose group. We concluded that dietary fructose enhances ANG II’s ability to stimulate renal proximal tubule Na+ reabsorption by augmenting PKC-α activation via elevated increases in intacellular Ca2+.

Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments

1991 ◽  
Vol 260 (1) ◽  
pp. F19-F26 ◽  
Author(s):  
M. C. Chobanian ◽  
C. M. Julin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Glucose Production ◽  
Renal Proximal Tubule ◽  
Ang Ii ◽  
Ammonia Production ◽  
Proximal Tubule Segments ◽  
Dependent Pathway ◽  
Stimulation Of

To determine whether angiotensin II (ANG II) affects ammoniagenesis in renal proximal tubule, ammonia production was measured in suspensions of canine renal proximal tubule segments (PCT) incubated with L-glutamine and varying concentrations of ANG II. Ammonia production from PCT was significantly increased by 15.5 +/- 1.1% in the presence of ANG II (10(-6) M) at 2 h. Similarly, glucose production significantly increased by 10.0 +/- 0.9%. Half-maximal stimulation occurred at approximately 10(-9) M ANG II. Stimulation of ammonia production by ANG II was blocked in the presence of the ANG II antagonist, [Sar1-Ile8]ANG II (10(-6) M). Enhancement of ammonia production in PCT by ANG II occurred in acidotic and neutral media but not in alkalotic medium. When extracellular [Na+] = intracellular [Na+] ANG II significantly increased ammonia production in PCT. Absence of extracellular Ca2+ or addition of trifluoperazine or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) (Ca2(+)-calmodulin-dependent pathway inhibitors) blocked the action of ANG II to enhance ammonia production. We conclude that ANG II stimulates ammonia and glucose production in canine renal PCT via a receptor-mediated signal. The action of ANG II on ammoniagenesis may be mediated by a calcium-calmodulin-dependent pathway. Stimulation of ammoniagenesis in vitro under normal and acidotic conditions may reflect a role in vivo for ANG II in the regulation of renal acid-base metabolism.

scholarly journals Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli

2010 ◽  
Vol 298 (1) ◽  
pp. F177-F186 ◽  
Author(s):  
Anne D. M. Riquier-Brison ◽  
Patrick K. K. Leong ◽  
Kaarina Pihakaski-Maunsbach ◽  
Alicia A. McDonough
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Enzyme Inhibitor ◽  
Volume Flow Rate ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Associated Proteins ◽  
Gradient Fractionation

Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water reabsorption. We showed that treating rats acutely with the angiotensin-converting enzyme inhibitor captopril decreases PT salt and water reabsorption and provokes rapid redistribution of the Na+/H+ exchanger isoform 3 (NHE3), Na+/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli. The aim of the present study was to determine whether acute ANG II infusion increases the abundance of PT NHE3, NaPi2, and associated proteins in the microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused with a dose of captopril (12 μg/min for 20 min) that increased PT flow rate ∼20% with no change in blood pressure (BP) or glomerular filtration rate (GFR). When ANG II (20 ng·kg−1·min−1 for 20 min) was added to the captopril infusate, PT volume flow rate returned to baseline without changing BP or GFR. After captopril, NHE3 was localized to the base of the microvilli and NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2 redistributed into the microvilli, assayed by confocal microscopy and density gradient fractionation. Additional PT proteins that redistributed into low-density microvilli-enriched membranes in response to ANG II included myosin VI, DPPIV, NHERF-1, ezrin, megalin, vacuolar H+-ATPase, aminopeptidase N, and clathrin. In summary, in response to 20 min ANG II in the absence of a change in BP or GFR, multiple proteins traffic into the PT brush-border microvilli where they likely contribute to the rapid increase in PT salt and water reabsorption.

scholarly journals Proximal Tubule-Specific Deletion of Angiotensin II Type 1a Receptors in the Kidney Attenuates Circulating and Intratubular Angiotensin II–Induced Hypertension in PT- Agtr1a −/− Mice

Hypertension ◽  
2021 ◽  
Author(s):  
Xiao Chun Li ◽  
Ana Paula Oliveira Leite ◽  
Xiaowen Zheng ◽  
Chunling Zhao ◽  
Xu Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fusion Protein ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Normal Blood ◽  
Ang Ii ◽  
Normal Blood Pressure ◽  
Wild Type ◽  
Induced Hypertension

The present study used a novel mouse model with proximal tubule-specific knockout of AT 1a receptors in the kidney, PT- Agtr1a −/− , to test the hypothesis that intratubular Ang II (angiotensin II) and AT 1a receptors in the proximal tubules are required for maintaining normal blood pressure and the development of Ang II–induced hypertension. Twenty-six groups (n=6–15 per group) of adult male wild-type, global Agtr1a −/− , and PT- Agtr1a −/− mice were infused with Ang II (1.5 mg/kg per day, IP), or overexpressed an intracellular Ang II fusion protein in the proximal tubules for 2 weeks. Basal telemetry blood pressure were ≈15±3 mm Hg lower in PT- Agtr1a −/− than wild-type mice and ≈13±3 mm Hg higher than Agtr1a −/− mice ( P <0.01). Basal glomerular filtration was ≈23.9% higher ( P <0.01), whereas fractional proximal tubule Na + reabsorption was lower in PT- Agtr1a −/− mice ( P <0.01). Deletion of AT 1a receptors in the proximal tubules augmented the pressure-natriuresis response ( P <0.01) and natriuretic responses to salt loading or Ang III infusion ( P <0.01). Ang II induced hypertension in wild-type, PT- Agtr1a −/− and PT- Nhe3 −/− mice, but the pressor response was ≈16±2 mm Hg lower in PT- Agtr1a −/− and PT- Nhe3 −/− mice ( P <0.01). Deletion of AT 1a receptors or NHE3 (Na + /H + exchanger 3) in the proximal tubules attenuated ≈50% of Ang II–induced hypertension in wild-type mice ( P <0.01), but blocked intracellular Ang II fusion protein-induced hypertension in PT- Agtr1a −/− mice ( P <0.01). Taken together, the results of the present study provide new insights into the critical role of intratubular Ang II/AT 1 (AT 1a )/NHE3 pathways in the proximal tubules in normal blood pressure control and the development of Ang II–induced hypertension.

Abstract 41: Fructose Stimulates Na/H Exchanger 3 Activity and Enhances the Ability of Angiotensin II to Activate Na/H Exchanger 3 in the Proximal Tubule

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pablo Cabral ◽  
Nancy Hong ◽  
Jeffrey Garvin
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Physiological Saline ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Basal Rate ◽  
Low Concentrations ◽  
Sprague Dawley Rats ◽  
High Fructose ◽  
Salt Sensitive Hypertension

Consumption of high-fructose corn syrup as a sweetener has increased dramatically. Fructose has been implicated in the epidemic of diabetes, obesity and hypertension including salt-sensitive hypertension. However, the mechanisms are poorly understood. The proximal nephron reabsorbs 60-70% of the fluid and Na, and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport has been implicated in several forms of hypertension. We hypothesized that fructose stimulates NHE3 activity and enhances the ability of angiotensin II (ANG II) to activate NHE3 in the proximal tubule. To test our hypothesis we isolated and perfused proximal tubules from Sprague Dawley rats. NHE3 activity was measured as the recovery of intracellular pH after an NH4Cl acid pulse using the pH sensitive dye BCECF. The rate of pH recovery was measured in Fluorescent Units per second (FU/sec). In the presence of a 5.5 mM glucose-containing physiological saline the basal rate of pH recovery was 3.1 ± 0.8 FU/sec. When the luminal solution was exchanged to a 0.6 mM glucose + 5 mM fructose-containing physiological saline in a second period, the rate of pH recovery increased to 5 ± 1 FU/sec (p<0.03, n=8).To study whether this effect was due to the addition of fructose or the removal of glucose to the lumen, we performed a separate set of experiments where 5 mM glucose was substituted for 5 mM fructose. In the presence of 0.6 mM glucose the basal rate of pH recovery was 3.6 ± 1.5 FU/sec. When 5 mM fructose was added the rate of pH recovery increased to 5.9 ± 2 FU/sec (p<0.02, n=5). Control experiments showed no differences between periods when 5 mm glucose was added back to the luminal perfusate. Finally, we tested the effect of low concentrations of ANG II in the presence or absence of luminal fructose. In the presence of 5.5 mM glucose, ANG II 10-12 M did not affect the rate of pH recovery (change: -1.1 ± 0.5 FU/sec, n=9). However, in the presence of 5 mM fructose, ANG II increased the rate of pH recovery (change: 4.0 ± 2.2 FU/sec, p< 0.03 n=6). We conclude that acute treatment with fructose stimulates NHE3 activity and enhances the ability of ANG II to activate NHE3 in the proximal tubule. These results may partially explain the mechanism by which a fructose diet induces hypertension.

Abstract 065: Overexpression of an Intracellular Angiotensin II Fusion Protein Selectively in the Mitochondria of the Proximal Tubules Elevates Blood Pressure in Mice via AT 1a Receptor-mediated Mitochondrial Respiratory and Glycolysis Stress

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Manoocher Soleimani ◽  
Hoang Nguyen ◽  
Hong Li ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fusion Protein ◽  
Proximal Tubule ◽  
Physiological Role ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Stress Tests ◽  
Arterial Blood ◽  
Mitochondrial Respiratory

An intracrine mitochondrial renin-angiotensin system (RAS) has recently been identified in various animal and human tissues, but whether the mitochondrial RAS plays a physiological role in the regulation of blood pressure remains unknown. The present study tested whether overexpression of an intracellular angiotensin II fusion protein, ECFP/ANG II, selectively in the mitochondria of the proximal tubules alters blood pressure, and whether the effects may involve AT 1a receptors and the Na + /H + exchanger 3 (NHE3). An adenoviral vector encoding ECFP/ANG II, a mitochondria targeting sequence, and the sglt2 promoter, Ad-sglt2-mito-ECFP/ANG II, was constructed for proximal tubule- and mitochondria-specific overexpression for 2 weeks. In adult male C57BL/6J mice, overexpression of mito-ECFP/ANG II in the mitochondria of the proximal tubules increased systolic blood pressure (SBP) significantly (Control: 116 ± 3 vs. mito-ECFP/ANG II: 128 ± 3 mmHg; p <0.01, n=15). The blood pressure-increasing effect of Ad-sglt2-mito-ECFP/ANG II was blocked in proximal tubule-specific AT 1a -KO mice (Control: 105 ± 2 vs. mito-ECFP/ANG II: 104 ± 4 mmHg; n.s ., n=7), or in proximal tubule-specific NHE3-KO mice (Control: 108 ± 3 vs. mito-ECFP/ANG II: 107 ± 3 mmHg; n.s ., n=13), respectively. In further experiments, mouse proximal tubule cells were transfected with Ad-sglt2-mito-ECFP/ANG II for 48 h and treated with the AT 1 blocker losartan (10 μM) or the AT 2 blocker PD123319 (10 μM) to measure mitochondrial respiratory and glycolytic function using Seahorse XF Cell Mito and XF Glycolysis Stress Tests. The mito-ECFP/ANG II expression was robust and colocalized with MitoTracker® Red FM. Overexpression of mito-ECFP/ANG II markedly increased oxygen consumption rate (OCR) (Control: 139.4 ± 9.2 vs. mito-ECFP/ANG II: 236.3 ± 12.6 pmol/min; p <0.01, n=12) and extracellular acidification rate (ECAR) (Control: 8.8 ± 0.6 vs. mito-ECFP/ANG II: 11.8 ± 1.2 mpH/min; p <0.01, n=12), respectively. Losartan blocked the effects of mito-ECFP/ANG II on OCR and ECAR, whereas PD123319 had no effect. We conclude that intracellular ANG II may activate AT 1 receptors in the mitochondria of the proximal tubules to alter mitochondrial respiratory and glycolytic function and arterial blood pressure.

Abstract P041: Proximal Tubule-specific Deletion Of Angiotensin Ii Type 1a Receptors In The Kidney Lowers Basal Blood Pressure And Attenuates Angiotensin Ii-induced Hypertension By Increasing Glomerular Filtration And The Pressure-natriuresis Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Ana P Leite ◽  
Liang Zhang ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Pressor Response ◽  
Control Group ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Basal Blood Pressure ◽  
Pressure Natriuresis ◽  
Specific Deletion

The present study tested the hypothesis that intratubular angiotensin II (Ang II) and AT 1a receptors in the proximal tubules of the kidney plays an important role in basal blood pressure control and in the development of Ang II-induced hypertension. Mutant mice with proximal tubule-specific deletion of AT 1a receptors in the kidney, PT- Agtr1a -/- , were generated to test the hypothesis. Eight groups (n=7-12 per group) of adult male wild-type (WT) and PT- Agtr1a -/- mice were infused with or without Ang II for 2 weeks (1.5 mg/kg, i.p.). Basal systolic, diastolic, and mean arterial pressures were ~13 ± 3 mmHg lower in PT- Agtr1a -/- than WT mice ( P <0.01). Basal glomerular filtration rate (GFR), as measured using transdermal FITC-sinistrin, was significantly higher in PT- Agtr1a -/- mice (WT: 160.4 ± 7.0 μl/min vs. PT- Agtr1a -/- : 186.0 ± 6.0 μl/min, P <0.05). Basal 24 h urinary Na + excretion (U Na V) was significantly higher in PT- Agtr1a -/- than WT mice ( P <0.01). In response to Ang II infusion, both WT and PT- Agtr1a -/- mice developed hypertension, and the magnitude of the pressor response to Ang II was similar in WT (Δ43 ± 3 mmHg, P <0.01) and PT- Agtr1a -/- mice (Δ39 ± 5 mmHg, P <0.01). However, the absolute blood pressure level was still 16 ± 3 mmHg lower in PT- Agtr1a -/- mice ( P <0.01). Ang II significantly decreased GFR to 132.2 ± 7.0 μl/min in WT mice ( P <0.01), and to 129.4 ± 18.6 μl/min in PT- Agtr1a -/- mice ( P <0.01), respectively. In WT mice, U Na V increased from 139.3 ± 22.3 μmol/24 h in the control group to 196.4 ± 29.6 μmol/24 h in the Ang II-infused group ( P <0.01). In PT- Agtr1a -/- mice, U Na V increased from 172.0 ± 10.2 μmol/24 h in the control group to 264.7 ± 35.4 μmol/24 h in the Ang II-infused group ( P <0.01). The pressor response to Ang II was attenuated, while the natriuretic response was augmented by losartan in WT and PT- Agtr1a -/- mice ( P <0.01). Finally, proximal tubule-specific deletion of AT 1a receptors significantly augmented the pressure-natriuresis response and natriuretic responses to acute saline infusion ( P <0.01) or a 2% high salt diet ( P <0.01). We concluded that deletion of AT 1a receptors selectively in the proximal tubules lowers basal blood pressure and attenuates Ang II-induced hypertension by increasing GFR and promoting the natriuretic response in PT- Agtr1a -/- mice.

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