Effect of luminal angiotensin II on ammonia production and secretion by mouse proximal tubules

Angiotensin II is an important regulator of acid-base and ammonia metabolism in the proximal tubule. Because angiotensin II receptors exist on the apical membrane and because luminal fluid angiotensin II concentrations may be substantial, the effects of luminal angiotensin II on ammonia production rates and net luminal total ammonia (tNH3) secretion rates were examined in dissected mouse S2 proximal tubule segments. Ammonia production rates reflected the total release of ammonia via the basolateral and luminal aspects of the tubule, whereas net luminal secretion rates reflected the rates at which ammonia left the tubule via the luminal fluid leaving the distal end of the perfused segment. The results demonstrated that 1) luminal angiotensin II affected tNH3 production in a concentration-dependent fashion, 2) luminal angiotensin II at concentrations that stimulated tNH3 production could counteract the effect of inhibitory basolateral concentrations of angiotensin II, 3) the stimulation of tNH3 production and the rise in intracellular calcium concentration induced by 10(-10) M luminal angiotensin II were blocked by the addition of an angiotensin II receptor inhibitor, saralasin, or the calcium channel blocker nifedipine to the luminal perfusion solution, and 4) in contrast to basolateral angiotensin II, which inhibited net luminal tNH3 secretion, luminal angiotensin II stimulated amiloride-sensitive net luminal tNH3 secretion in parallel with stimulation of luminal fluid acidification. Thus luminal angiotensin II at physiological and superphysiological concentrations has important effects on ammonia production and transport in the proximal tubule that in some ways differ from the effects of basolateral angiotensin II.

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Ammonia production and secretion by S3 proximal tubule segments from acidotic mice: role of ANG II

AJP Renal Physiology ◽

10.1152/ajprenal.00189.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. F707-F712 ◽

Cited By ~ 21

Author(s):

Glenn T. Nagami

Keyword(s):

Proximal Tubule ◽

Ang Ii ◽

Ammonia Production ◽

Low Sodium ◽

Luminal Perfusion ◽

And Control ◽

Acid Loading ◽

Proximal Tubule Segments ◽

Secretion Rates

ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH4Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice. By contrast, when ANG II was present in the luminal perfusion solution, ammonia production and secretion rates were stimulated, in a losartan-inhibitable manner, to a greater extent in S3 segments from acidotic mice. Ammonia secretion rates in S3 segments were largely inhibited by perfusion with a low-sodium solution containing amiloride in the presence or absence of ANG II. These results demonstrated that isolated, perfused mouse S3 proximal tubule segments produce and secrete ammonia, that NH4Cl-induced acidosis does not affect the basal rates of ammonia production and secretion, and that ANG II, added to the luminal fluid, stimulates ammonia production and secretion to a greater extent in S3 segments from acidotic mice. These findings suggest that S3 segments, in the presence of ANG II, can contribute to the enhanced renal excretion that occurs with acid loading.

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Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments

AJP Renal Physiology ◽

10.1152/ajprenal.1991.260.1.f19 ◽

1991 ◽

Vol 260 (1) ◽

pp. F19-F26 ◽

Cited By ~ 8

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.

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Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis

AJP Renal Physiology ◽

10.1152/ajprenal.00286.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. F874-F880 ◽

Cited By ~ 28

Author(s):

Glenn T. Nagami

Keyword(s):

Metabolic Acidosis ◽

Angiotensin Ii ◽

Proximal Tubule ◽

Phosphoenolpyruvate Carboxykinase ◽

Ammonia Excretion ◽

Angiotensin Ii Receptor Blocker ◽

Ammonia Production ◽

Angiotensin Ii Receptor ◽

Proximal Tubule Segments

Acidosis and angiotensin II stimulate ammonia production and transport by the proximal tubule. We examined the modulatory effect of the type 1 angiotensin II receptor blocker losartan on the ability of metabolic acidosis to stimulate ammonia production and secretion by mouse S2 proximal tubule segments. Mice given NH4Cl for 7 days developed metabolic acidosis (low serum bicarbonate concentration) and increased urinary excretion of ammonia. S2 tubule segments from acidotic mice displayed higher rates of ammonia production and secretion compared with those from control mice. However, when losartan was coadministered in vivo with NH4Cl, both the acidosis-induced increase in urinary ammonia excretion and the adaptive increase in ammonia production and secretion of microperfused S2 segments were largely blocked. In renal cortical tissue, losartan blocked the acid-induced increase in brush-border membrane NHE3 expression but had no effect on the acid-induced upregulation of phosphate-dependent glutaminase or phosphoenolpyruvate carboxykinase 1 in cortical homogenates. Addition of angiotensin II to the microperfusion solution enhanced ammonia secretion and production rates in tubules from NH4Cl-treated and control mice in a losartan-inhibitable manner. These results demonstrate that a 7-day acid challenge induces an adaptive increase in ammonia production and secretion by the proximal tubule and suggest that during metabolic acidosis, angiotensin II signaling is necessary for adaptive enhancements of ammonia excretion by the kidney and ammonia production and secretion by S2 proximal tubule segments, as mediated, in part, by angiotensin receptor-dependent enhancement of NHE3 expression.

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Enhanced ammonia secretion by proximal tubules from mice receiving NH4Cl: role of angiotensin II

AJP Renal Physiology ◽

10.1152/ajprenal.00249.2001 ◽

2002 ◽

Vol 282 (3) ◽

pp. F472-F477 ◽

Cited By ~ 18

Author(s):

Glenn T. Nagami ◽

Keyword(s):

Angiotensin Ii ◽

Proximal Tubule ◽

Ang Ii ◽

Ammonia Production ◽

Short Term ◽

Adaptive Enhancement ◽

And Control ◽

Secretion Rates

Acidosis and angiotensin II (ANG II) stimulate ammonia production and transport by the proximal tubule. We examined the effect of short-term (18 h) in vivo acid loading with NH4Cl on ammonia production and secretion rates by mouse S2 proximal tubule segments microperfused in vitro with or without ANG II in the luminal microperfusion solution. S2 tubules from NH4Cl-treated mice displayed higher rates of luminal ammonia secretion compared with those from control mice. The adaptive increase in ammonia secretion in NH4Cl-treated mice was eliminated when losartan was coadministered in vivo with NH4Cl. Ammonia secretion rates from both NH4Cl-treated and control mice were largely inhibited by amiloride. Addition of ANG II to the microperfusion solution enhanced ammonia secretion and production rates to a greater extent in tubules from NH4Cl-treated mice compared with those from controls, and the stimulatory effects of ANG II were blocked by losartan. These results demonstrate that a short-term acid challenge induces an adaptive increase in ammonia secretion by the proximal tubule and suggest that ANG II plays an important role in the adaptive enhancement of ammonia secretion that is observed with short-term acid challenges.

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