Inhibitory effect of angiotensin II on renal tubular transport

1991 ◽  
Vol 260 (3) ◽  
pp. F340-F346 ◽  
Author(s):  
V. Chatsudthipong ◽  
Y. L. Chan
Keyword(s):  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Inhibitory Effects ◽  
High Concentration ◽  
Extracellular Medium ◽  
Peritubular Capillaries ◽  
Tubular Transport ◽  
Proximal Tubular ◽  
High Concentrations

This study was designed to examine the intracellular mechanism of inhibitory action of high concentration of angiotensin II (ANG II) on proximal tubular transport in rat kidneys by microperfusion methods. Perfusion of ANG II (10(-6) M) to peritubular capillaries caused a reduction of both fluid and HCO3- transport (Jv and JHCO3-, respectively) by 33 and 26%, respectively. These inhibitory effects were blocked by the ANG II-receptor antagonist [Sar1, Ile8]ANG II (10(-5) M). Similar degrees of inhibition on Jv and JHCO3- were observed when ionomycin (10(-7) and 10(-6) M), a Ca2+ ionophore, was added to capillary perfusate. Moreover, there was no additive effect when both ANG II and ionomycin were perfused together through capillaries, suggesting that both agents work via the same mechanism, presumably by increasing cytosolic Ca2+ concentration ([Ca2+]i). Inhibitory effects of ANG II on proximal tubular transport were still observed in a Ca2(+)-free perfusate containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, indicating that these effects do not require influx of Ca2+ from extracellular medium. Furthermore, the observation that TMB-8, an agent that prevents intracellular Ca2+ mobilization, completely eliminated the effect of ANG II strongly suggests that intracellular Ca2+ rather than Ca2+ influx mediates effects of ANG II on proximal tubular transport. Direct measurement of [Ca2+]i by use of fura-2 in isolated proximal tubular cells showed slight but statistically significant increases in [Ca2+]i. Taken together, these observations support the idea that intracellular Ca2+ serves as a second messenger in the inhibitory effect of high concentrations of ANG II on Jv and JHCO3- in proximal tubule of kidney.

Angiotensin II-mediated biphasic regulation of proximal tubular Na+/H+ exchanger 3 is impaired during oxidative stress

2011 ◽  
Vol 301 (2) ◽  
pp. F364-F370 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Tap Water ◽  
Buthionine Sulfoximine ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Sprague Dawley ◽  
High Concentration ◽  
Nitric Oxide Signaling ◽  
Proximal Tubular

Angiotensin (ANG) II via AT1 receptors (AT1Rs) maintains sodium homeostasis by regulating renal sodium transporters including Na+/H+ exchanger 3 (NHE3) in a biphasic manner. Low-ANG II concentration stimulates whereas high concentrations inhibit NHE3 activity. Oxidative stress has been shown to upregulate AT1R function that could modulate the ANG II-mediated NHE3 regulation. This study was designed to identify the signaling pathways responsible for ANG II-mediated biphasic regulation of proximal tubular NHE3 and the effect of oxidative stress on this phenomenon. Male Sprague-Dawley rats were chronically treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol in tap water for 3 wk. BSO-treated rats exhibited oxidative stress and high blood pressure. At low concentration (1 pM) ANG II increased NHE3 activity in proximal tubules from all animals. However, in BSO-treated rats, the stimulation was more robust and was normalized by tempol treatment. ANG II (1 pM)-mediated NHE3 activation was abolished by AT1R blocker, intracellular Ca2+ chelator, and inhibitors of phospholipase C (PLC) and Ca2+-dependent calmodulin (CaM) but it was insensitive to Giα and protein kinase C inhibitors or AT2R antagonist. A high concentration of ANG II (1 μM) inhibited NHE3 activity in control and tempol-treated rats. However, in BSO-treated rats, ANG II (1 μM) continued to induce NHE3 stimulation. Tempol restored the inhibitory effect of ANG II (1 μM) in BSO-treated rats. The inhibitory effect of ANG II (1 μM) involved AT1R-dependent, cGMP-dependent protein kinase (PKG) activation and was independent of AT2 receptor and nitric oxide signaling. We conclude that ANG II stimulates NHE3 via AT1R-PLC-CaM pathway and inhibits NHE3 by AT1R-PKG activation. Oxidative stress impaired ANG II-mediated NHE3 biphasic response in that stimulation was observed at both high- and low-ANG II concentration.

Potentiation of Adrenaline-Induced Platelet Aggregation by Angiotensin II

1985 ◽  
Vol 54 (03) ◽  
pp. 717-720 ◽  
Author(s):  
Yu-An Ding ◽  
D Euan MacIntyre ◽  
Christopher J Kenyon ◽  
Peter F Semple
Keyword(s):  
Platelet Aggregation ◽  
Angiotensin Ii ◽  
Human Platelet ◽  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
Ang Ii ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
High Concentrations ◽  
Stimulation Of

SummaryThe effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10™11 - 10™7 M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (<2 min) or longterm (30 min) incubation. In contrast, low concentrations of ANG II (10™11 M) enhanced adrenaline-induced platelet aggregation but high concentrations (10™7 M) had an inhibitory effect. Moreover, ANG II (10™11 - 10™7 M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2

Angiotensin II mediates drinking elicited by eating in the rat

1990 ◽  
Vol 258 (2) ◽  
pp. R436-R442 ◽  
Author(s):  
F. S. Kraly ◽  
R. Corneilson
Keyword(s):  
Angiotensin Ii ◽  
Drinking Behavior ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Inhibitory Effects ◽  
Physiological Conditions ◽  
Sprague Dawley Rats ◽  
Subcutaneous Dose ◽  
H2 Receptors

Captopril (CA) was used to block synthesis of endogenous angiotensin II (ANG II) in periphery and/or brain of adult male Sprague-Dawley rats in tests for drinking elicited by eating pelleted chow. Blockade of ANG II-converting enzyme (ACE) in periphery alone (using 0.5 mg/kg CA) increased drinking elicited by eating, whereas simultaneous blockade of ACE in periphery and brain (using subcutaneous 100 mg/kg CA or subcutaneous 0.5 mg/kg plus third ventricular 25 micrograms CA) decreased such drinking. The inhibitory effect of 100 mg/kg CA on water-to-food ratio was prevented by a dipsogenically subthreshold subcutaneous dose (5 micrograms/kg) of ANG II. Blockade of ACE in brain alone (third ventricular 25 micrograms CA) had no effect on food-related drinking. Pharmacological antagonism of ANG II (100 mg/kg CA) together with antagonism of histamine H1 and H2 receptors (using intraperitoneal dexbrompheniramine and cimetidine) were not additive in their inhibitory effects on drinking elicited by eating. Blockade of ACE (100 mg/kg CA) inhibited drinking elicited by subcutaneous histamine, but blockade of histamine receptors failed to inhibit drinking elicited by subcutaneous ANG II. These results support a role for endogenous ANG II under what appear to be physiological conditions for drinking behavior, i.e., when drinking is elicited by eating, and they suggest the working hypothesis of ANG II mediation of a histaminergic mechanism for food-related drinking in the rat.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line

1989 ◽  
Vol 257 (5) ◽  
pp. C888-C895 ◽  
Author(s):  
E. Coezy ◽  
I. Darby ◽  
J. Mizrahi ◽  
B. Cantau ◽  
M. H. Donnadieu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Ang Ii ◽  
Hep G2 ◽  
Dose Dependent

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

Mechanisms of angiotensin II natriuresis and antinatriuresis

1985 ◽  
Vol 249 (2) ◽  
pp. F299-F307 ◽  
Author(s):  
M. E. Olsen ◽  
J. E. Hall ◽  
J. P. Montani ◽  
A. C. Guyton ◽  
H. G. Langford ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Distal Tubule ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Anesthetized Dogs

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of atrial natriuretic factor and angiotensin II in proximal HCO3- reabsorption

1992 ◽  
Vol 262 (2) ◽  
pp. F303-F308 ◽  
Author(s):  
G. N. Gomes ◽  
M. M. Aires
Keyword(s):  
Angiotensin Ii ◽  
Atrial Natriuretic Factor ◽  
Control Group ◽  
Ang Ii ◽  
Half Time ◽  
Capillary Perfusion ◽  
Perfusion Fluid ◽  
Natriuretic Factor ◽  
Peritubular Capillaries ◽  
Atrial Natriuretic

Bicarbonate reabsorption was evaluated by the acidification kinetics technique in middle proximal tubule in Munich-Wistar rats. Atrial natriuretic factor (ANF) and angiotensin II (ANG II) were infused into the jugular vein (ANF, 0.5 microgram.min-1.kg-1 after a prime of 10 micrograms/kg; ANG II, 20 ng.min-1.kg-1) or added to luminal or peritubular perfusion fluid (10(-6) M ANF; 10(-12) M ANG II). In the presence of ANF, in each condition, no significant differences in net HCO3- reabsorption or in acidification half time were observed compared with the control group. In the presence of ANG II, a significant increase in HCO3- reabsorption was observed, expressed by a fall in acidification half time from a mean of 4.75 +/- 0.20 (n = 86) to 2.47 +/- 0.18 s (n = 32) in systemically infused rats or to 2.30 +/- 0.15 s (n = 35) in luminally perfused tubules and from 4.57 +/- 0.32 (n = 44) to 2.04 +/- 0.10 s (n = 50) during capillary perfusion. However, when ANG II was systemically infused or perfused in lumen or in peritubular capillaries, addition of ANF to lumen or capillaries by perfusion or systemic infusion abolished the effects observed with ANG II alone. These studies confirm that ANG II stimulates proximal HCO3- reabsorption and show that ANF alone does not affect this process, but impairs the stimulation caused by ANG II.

Effects of angiotensin II on proximal tubular cells stably transfected with the c-mas oncogene

1992 ◽  
Vol 263 (5) ◽  
pp. F931-F938 ◽  
Author(s):  
G. Wolf ◽  
E. G. Neilson
Keyword(s):  
Angiotensin Ii ◽  
De Novo ◽  
Cell Phenotype ◽  
Scatchard Analysis ◽  
Tubular Epithelium ◽  
Ang Ii ◽  
Protein Signaling ◽  
Signaling Mechanism ◽  
Cellular Hypertrophy ◽  
Proximal Tubular

Angiotensin II (ANG II) normally induces cellular hypertrophy in proximal tubular epithelium by engaging receptor systems that use a G-protein-signaling mechanism. The c-mas oncogene also encodes part of a superfamily of vasoactive peptide receptor-like moieties that couple to G proteins. To determine whether the stable expression of the c-mas gene might alter or modify the induction of cellular hypertrophy by ANG II in tubular epithelium, a rat c-mas cDNA was cloned into the pSV2 expression vector for use in cell transfection. Scatchard analysis of ANG II binding revealed no significant differences in ANG II receptor number or in the dissociation constant between pSV2mas-transfected or wild-type MCT cells, but rather an increase in the number of receptors not replaceable by known inhibitors. ANG II also induced proliferation in pSV2mas-transfected MCT cells that was not blocked by conventional inhibitors and increased intracellular levels of inositol trisphosphate. ANG II, furthermore, did not increase de novo protein synthesis in pSV2-transfected MCT cells and failed to lower their intracellular concentration of adenosine 3',5'-cyclic monophosphate, both expected parameters of cellular hypertrophy. Our findings demonstrate that expression of c-mas in tubular epithelium can modulate tubular cell phenotype toward proliferation rather than hypertrophy. This effect is likely mediated by a reshuffling of the heterogeneity of ANG II receptors on the cell surface, or perhaps by the emergence of a new ANG II receptor, followed by alterations in the process of signal transduction.

Inhibitory effects of DuP 753 and EXP3174 on responses to angiotensin II in pulmonary vascular bed of the cat

1992 ◽  
Vol 73 (5) ◽  
pp. 2054-2061 ◽  
Author(s):  
T. J. McMahon ◽  
A. D. Kaye ◽  
J. S. Hood ◽  
R. K. Minkes ◽  
B. D. Nossaman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Inhibitory Effect ◽  
Response Relationship ◽  
Norepinephrine Release ◽  
Inhibitory Effects ◽  
Dose Response Relationship ◽  
Vascular Bed ◽  
The Right ◽  
Pulmonary Vascular Bed

The effects of the non-peptide antagonist DuP 753 and its metabolite EXP3174 on responses to angiotensin II were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, injections of angiotensin II into the perfused lobar artery caused dose-related increases in lobar arterial pressure. Responses to angiotensin II were reproducible and were not changed by meclofenamate or prazosin, indicating that prostaglandin or norepinephrine release does not mediate or modulate pulmonary vascular responses to the peptide. DuP 753 (1–5 mg/kg iv) decreased responses to angiotensin II in a competitive manner, and the duration of the blockade was related to dose of the antagonist. DuP 753 had no significant effect on responses to U-46619, norepinephrine, serotonin, endothelin-1, vasopressin, or BAY K 8644. EXP3174 also decreased responses to angiotensin II without altering responses to agents that act by a variety of mechanisms. The inhibitory effect of EXP3174 (1 mg/kg iv) was not overcome by angiotensin II in the range of doses studied, and the shift to the right of the dose-response curve was nonparallel, suggesting that the blockade was noncompetitive. The blockade was long in duration, and, when the dose of EXP3174 was decreased to 0.1 mg/kg iv, the blockade was surmounted and the shift to the right of the dose-response relationship was parallel. DuP 753 and EXP3174 had little effect on mean baseline pressures in the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic studies on transport of PAH and other organic acids in isolated renal tubules

1965 ◽  
Vol 208 (2) ◽  
pp. 391-396 ◽  
Author(s):  
K. C. Huang ◽  
Dorothy S. T. Lin
Keyword(s):  
Organic Acids ◽  
Partition Coefficient ◽  
Transport Mechanism ◽  
Hippuric Acid ◽  
Kinetic Studies ◽  
Inhibitory Effect ◽  
Renal Tubules ◽  
High Concentration ◽  
Low Concentration ◽  
Tubular Transport

Studies were made on the uptake and washout of PAH and other organic acids in isolated renal tubules and cells at 25 C. The renal tubules accumulated PAH rapidly in the first 30-min period. Probenecid, its diethyl- and dimethyl analogues, hippuric acid, and 2,4-dinitrophenol inhibited the tubular transport of PAH competitively. A relationship between the inhibitory effect and the partition coefficient of the compound was observed; the higher the partition coefficient, the greater the inhibition. DNP was also accumulated in the isolated renal tubules. This accumulation was depressed by probenecid, indicating that DNP is probably transported by the same tubular transport mechanism for PAH and other organic acids. In washout experiments probenecid and DNP showed a biphasic action, namely, they stimulated the PAH washout in low concentration and inhibited it in high concentration However, hippuric acid, which has a low partition coefficient, demonstrated an augmentation of PAH washout even at a concentration of 2 x 10–2 m

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