scholarly journals Modulation of outer medullary NaCl transport and oxygenation by nitric oxide and superoxide

2011 ◽  
Vol 301 (5) ◽  
pp. F979-F996 ◽  
Author(s):  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Active Transport ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Complex Interactions ◽  
Medullary Thick Ascending Limb ◽  
The Impact ◽  
Stimulation Of

We expanded our region-based model of water and solute exchanges in the rat outer medulla to incorporate the transport of nitric oxide (NO) and superoxide (O2−) and to examine the impact of NO-O2− interactions on medullary thick ascending limb (mTAL) NaCl reabsorption and oxygen (O2) consumption, under both physiological and pathological conditions. Our results suggest that NaCl transport and the concentrating capacity of the outer medulla are substantially modulated by basal levels of NO and O2−. Moreover, the effect of each solute on NaCl reabsorption cannot be considered in isolation, given the feedback loops resulting from three-way interactions between O2, NO, and O2−. Notwithstanding vasoactive effects, our model predicts that in the absence of O2−-mediated stimulation of NaCl active transport, the outer medullary concentrating capacity (evaluated as the collecting duct fluid osmolality at the outer-inner medullary junction) would be ∼40% lower. Conversely, without NO-induced inhibition of NaCl active transport, the outer medullary concentrating capacity would increase by ∼70%, but only if that anaerobic metabolism can provide up to half the maximal energy requirements of the outer medulla. The model suggests that in addition to scavenging NO, O2− modulates NO levels indirectly via its stimulation of mTAL metabolism, leading to reduction of O2 as a substrate for NO. When O2− levels are raised 10-fold, as in hypertensive animals, mTAL NaCl reabsorption is significantly enhanced, even as the inefficient use of O2 exacerbates hypoxia in the outer medulla. Conversely, an increase in tubular and vascular flows is predicted to substantially reduce mTAL NaCl reabsorption. In conclusion, our model suggests that the complex interactions between NO, O2−, and O2 significantly impact the O2 balance and NaCl reabsorption in the outer medulla.

Potassium deprivation upregulates expression of renal basolateral Na+-HCO3 −cotransporter (NBC-1)

2000 ◽  
Vol 279 (3) ◽  
pp. F532-F543 ◽  
Author(s):  
Hassane Amlal ◽  
Khalid Habo ◽  
Manoocher Soleimani
Keyword(s):  
Proximal Tubule ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Time Intervals ◽  
Outer Medulla ◽  
Medullary Thick Ascending Limb ◽  
Medullary Collecting Duct ◽  
Potassium Deprivation ◽  
Expression And Activity

The purpose of the present experiments was to examine the effect of potassium deprivation on the expression of the renal basolateral Na+-HCO3 − cotransporter (NBC-1). Rats were placed on a K+-free diet for various time intervals and examined. NBC-1 mRNA levels increased by about threefold in the cortex ( P < 0.04) at 72 h of K+ deprivation and remained elevated at 21 days. NBC activity increased by ∼110% in proximal tubule suspensions, with the activity increasing from 0.091 in control to 0.205 pH/min in the K+-deprived group ( P < 0.005). The inner stripe of outer medulla and cells of medullary thick ascending limb of Henle (mTAL) showed induction of NBC-1 mRNA and activity in K+-deprived rats, with the activity in mTAL increasing from 0.010 in control to 0.133 pH/min in the K+-deprived group ( P < 0.004). K+ deprivation also increased NBC-1 mRNA levels in the renal papilla ( P < 0.02). We conclude that 1) K+ deprivation increases NBC-1 expression and activity in proximal tubule and 2) K+deprivation causes induction of NBC-1 expression and activity in mTAL tubule and inner medulla. We propose that NBC-1 likely mediates enhanced HCO3 − reabsorption in proximal tubule, mTAL, and inner medullary collecting duct in K+ deprivation and contributes to the maintenance of metabolic alkalosis in this condition.

scholarly journals Impact of renal medullary three-dimensional architecture on oxygen transport

2014 ◽  
Vol 307 (3) ◽  
pp. F263-F272 ◽  
Author(s):  
Brendan C. Fry ◽  
Aurélie Edwards ◽  
Ioannis Sgouralis ◽  
Anita T. Layton
Keyword(s):  
Oxygen Delivery ◽  
Interstitial Fluid ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Three Dimensional ◽  
Fluid Composition ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
The Impact

We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (Po2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial Po2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal Po2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the high metabolic requirements of the thick limbs and raises NaCl reabsorption.

Hyposmolality stimulates Na+/H+ exchange and HCO3 − absorption in thick ascending limb via PI 3-kinase

2000 ◽  
Vol 279 (5) ◽  
pp. C1443-C1454 ◽  
Author(s):  
David W. Good ◽  
John F. Di Mari ◽  
Bruns A. Watts
Keyword(s):  
Signal Transduction ◽  
Thick Ascending Limb ◽  
Phosphatidylinositol 3 Kinase ◽  
Outer Medulla ◽  
Medullary Thick Ascending Limb ◽  
Clinical Disorders ◽  
Transduction Mechanisms ◽  
Dependent Pathway ◽  
Stimulation Of

The signal transduction mechanisms that mediate osmotic regulation of Na+/H+ exchange are not understood. Recently we demonstrated that hyposmolality increases HCO3 − absorption in the renal medullary thick ascending limb (MTAL) through stimulation of the apical membrane Na+/H+ exchanger NHE3. To investigate the mechanism of this stimulation, MTALs from rats were isolated and perfused in vitro with 25 mM HCO3 −-containing solutions. The phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin (100 nM) and LY-294002 (20 μM) blocked completely the stimulation of HCO3 − absorption by hyposmolality. In tissue strips dissected from the inner stripe of the outer medulla, the region of the kidney highly enriched in MTALs, hyposmolality increased PI 3-K activity 2.2-fold. Wortmannin blocked the hyposmolality-induced PI 3-K activation. Further studies examined the interaction between hyposmolality and vasopressin, which inhibits HCO3 −absorption in the MTAL via cAMP and often is involved in the development of plasma hyposmolality in clinical disorders. Pretreatment with arginine vasopressin, forskolin, or 8-bromo-cAMP abolished hyposmotic stimulation of HCO3 − absorption, due to an effect of cAMP to inhibit hyposmolality- induced activation of PI 3-K. In contrast to their effects to block stimulation by hyposmolality, PI 3-K inhibitors and vasopressin have no effect on inhibition of apical Na+/H+ exchange (NHE3) and HCO3 − absorption by hyperosmolality. These results indicate that hyposmolality increases NHE3 activity and HCO3 − absorption in the MTAL through activation of a PI 3-K-dependent pathway that is inhibited by vasopressin and cAMP. Hyposmotic stimulation and hyperosmotic inhibition of NHE3 are mediated through different signal transduction mechanisms.

PGE2, forskolin, and cholera toxin interactions in modulating NaCl transport in mouse mTALH

1984 ◽  
Vol 247 (5) ◽  
pp. F784-F792 ◽  
Author(s):  
R. M. Culpepper ◽  
T. E. Andreoli
Keyword(s):  
Adenylate Cyclase ◽  
Cholera Toxin ◽  
Thick Ascending Limb ◽  
Nacl Transport ◽  
Medullary Thick Ascending Limb ◽  
Maximal Stimulation ◽  
Chloride Absorption ◽  
Receptor Interactions ◽  
Transepithelial Voltage ◽  
Stimulation Of

Prostaglandin E2 (PGE2) inhibits the ADH-stimulated components of the lumen-positive transepithelial voltage (Ve) and of net chloride absorption (JnetCl) in the isolated microperfused mouse medullary thick ascending limb of Henle (mTALH), presumably by interfering with the ADH-dependent intracellular accumulation of cAMP. These experiments examined the interactions of PGE2 with two nonhormonal stimulators of adenylate cyclase--cholera toxin and forskolin--in an attempt to evaluate the means by which PGE2 inhibits ADH-stimulated transport in these mTALH segments. Forskolin (FSK) stimulated Ve in the mTALH with half-maximal stimulation at 1.4 X 10(-7) M FSK. PGE2 had no effect on FSK stimulation of Ve; 10(-6) M FSK reversed completely the PGE2 inhibition of ADH-stimulated Ve. A low concentration of cholera toxin, 5 X 10(-13) M, stimulated Ve and JnetCl in the mTALH; 10(-6) M PGE2 inhibited the stimulation by cholera toxin; and 10(-6) M FSK reversed the PGE2 inhibition of both Ve and JnetCl in cholera toxin-stimulated mTALH. A higher concentration of cholera toxin, 10(-10) M, stimulated Ve and JnetCl to values identical to those seen with maximal concentrations of ADH, but PGE2 did not inhibit the increments in either Ve or JnetCl produced by 10(-10) M cholera toxin. PGE2 appears to inhibit ADH stimulation of NaCl transport in mTALH by an action distal to hormone-receptor interactions yet proximal to the catalytic subunit of adenylate cyclase.

scholarly journals Luminal angiotensin II stimulates rat medullary thick ascending limb chloride transport in the presence of basolateral norepinephrine

2016 ◽  
Vol 310 (4) ◽  
pp. F294-F299 ◽  
Author(s):  
Michel Baum
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Chloride Transport ◽  
Bathing Solution ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Nacl Transport ◽  
Medullary Thick Ascending Limb ◽  
Stimulation Of

Angiotensin II (ANG II) is secreted by the proximal tubule resulting in a luminal concentration that is 100- to 1,000-fold greater than that in the blood. Luminal ANG II has been shown to stimulate sodium transport in the proximal tubule and distal nephron. Surprisingly, luminal ANG II inhibits NaCl transport in the medullary thick ascending limb (mTAL), a nephron segment responsible for a significant amount of NaCl absorption from the glomerular ultrafiltrate. We confirmed that addition of 10−8 M ANG II to the lumen inhibited mTAL chloride transport (220 ± 19 to 165 ± 25 pmol·mm−1·min−1, P < 0.01) and examined whether an interaction with basolateral norepinephrine existed to simulate the in vivo condition of an innervated tubule. We found that in the presence of a 10−6 M norepinephrine bath, luminal ANG II stimulated mTAL chloride transport from 298 ± 18 to 364 ± 42 pmol·mm−1·min−1 ( P < 0.05). Stimulation of chloride transport by luminal ANG II was also observed with 10−3 M bath dibutyryl cAMP in the bathing solution and bath isoproterenol. A bath of 10−5 H-89 blocked the stimulation of chloride transport by norepinephrine and prevented the effect of luminal ANG II to either stimulate or inhibit chloride transport. Bath phentolamine, an α-adrenergic agonist, also prevented the decrease in mTAL chloride transport by luminal ANG II. Thus luminal ANG II increases chloride transport with basolateral norepinephrine; an effect likely mediated by stimulation of cAMP. Alpha-1 adrenergic stimulation prevents the inhibition of chloride transport by luminal ANG II.

Electrolyte, urea, and water transport in a two-nephron central core model of the renal medulla

1989 ◽  
Vol 257 (3) ◽  
pp. F399-F413 ◽  
Author(s):  
J. L. Stephenson ◽  
Y. Zhang ◽  
R. Tewarson
Keyword(s):  
Active Transport ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Volume Flow ◽  
Hydraulic Permeability ◽  
Significant Modification ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Alternative Mode ◽  
The Core

A one-nephron model has been extended to include both short-looped and long-looped nephrons. Variables are volume flow, Na+, K+, Cl-, urea, hydrostatic pressure, and electric potential. The ratio of short-to-long-looped nephrons, one of the parameters of the model, is 5 to 1. With either rabbit or hamster permeability data from perfusion experiments, the model develops an osmolality of approximately 600 mosmol/l at the junction of inner and outer medulla but no osmolality gradient in the inner medulla. With the rabbit data, osmolalities in excess of 1,000 mosmol/l can be generated in the papilla with no active transport if urea permeabilities are less than 10(-5) cm/s; with the hamster data, electrolyte permeabilities must also be reduced. With these modified parameters, urea concentrations are less in the long loops than has been found on micropuncture. These can be increased to experimental levels by increasing the urea permeability and decreasing the hydraulic permeability of thin descending limbs in the inner half of the inner medulla, but to maintain loop osmolality at 1,000 mosmol/l it is necessary to postulate active NaCl transport in thin ascending limbs in the outer half of the inner medulla. This gives an alternative mode of concentration without active transport in the inner half of the inner medulla, in which electrolytes diffuse out of and urea diffuses into both limbs of Henle's loop and mix in the core with urea and water entering from the collecting duct. Concentration in either mode requires significant modification of perfusion data.

Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb

2006 ◽  
Vol 291 (2) ◽  
pp. F350-F357 ◽  
Author(s):  
Michiaki Abe ◽  
Paul O'Connor ◽  
Mary Kaldunski ◽  
Mingyu Liang ◽  
Richard J. Roman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Flow Rate ◽  
Renal Medulla ◽  
Renal Perfusion ◽  
Thick Ascending Limb ◽  
Nacl Transport ◽  
Fluid Delivery ◽  
Tubular Necrosis ◽  
Medullary Thick Ascending Limb

Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl−. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.

scholarly journals Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice

2017 ◽  
Vol 313 (6) ◽  
pp. F1243-F1253 ◽  
Author(s):  
Minolfa C. Prieto ◽  
Virginia Reverte ◽  
Mykola Mamenko ◽  
Marta Kuczeriszka ◽  
Luciana C. Veiras ◽  
...  
Keyword(s):  
Renal Function ◽  
Collecting Duct ◽  
Ang Ii ◽  
Open Probability ◽  
Sodium Transporters ◽  
Prorenin Receptor ◽  
Active Channels ◽  
The Impact ◽  
Renal Responses ◽  
Stimulation Of

Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and renin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG II-dependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

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