Cellular action of arginine vasopressin in the isolated renal tubules of hypothyroid rats

1987 ◽  
Vol 253 (1) ◽  
pp. F104-F110 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Morphological Changes ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Urinary Volume ◽  
Outer Medulla ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Collecting Tubules

Hypothyroidism has been demonstrated to be associated with an impaired concentrating capacity and specific morphological changes in the thick ascending limbs. This study was performed to evaluate the cellular action of arginine vasopressin (AVP) in the isolated renal tubules from control (C) and hypothyroid (HT) rats. Hypothyroidism was induced by feeding aminotriazole for 4 wk. Urinary volume was higher in HT rats (C 13.5 +/- 0.9, HT 17.7 +/- 0.9 ml/24 h, P less than 0.005) and urinary osmolality was lower in HT rats (C 1,707 +/- 49, HT 1,229 +/- 35 mosmol/kgH2O, P less than 0.001). Plasma AVP levels were significantly higher in HT rats (C 1.93 +/- 0.59, HT 4.12 +2- 0.62 pg/ml, P less than 0.05), thus documenting AVP resistance. The adenylate cyclase response to AVP (10(-6) M) was significantly lower (P less than 0.02) in the medullary thick ascending limb of Henle's loop (mTALH) in HT (14.3 +/- 2.4 to 41.7 +/- 5.8 fm X 30 min-1 X mm-1, P less than 0.001) than in mTALH in C rats (14.4 +/- 2.8 to 110.1 +/- 24.9 fm X 30 min-1 X mm-1, P less than 0.001). In contrast, the adenylate cyclase response to AVP was not significantly different in collecting tubules of cortex, outer medulla, and inner medulla from C and HT rats, although a slight decrease in response to AVP was observed in cortical and outer medullary collecting tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration

1986 ◽  
Vol 251 (2) ◽  
pp. F266-F270 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
A. E. Erickson ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Urinary Concentration ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Sprague Dawley Rats ◽  
Collecting Tubules

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.

Effects of arginine vasopressin on the thin ascending limb of Henle's loop of hamsters

1982 ◽  
Vol 243 (2) ◽  
pp. F167-F172 ◽  
Author(s):  
M. Imai ◽  
E. Kusano
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Chloride Transport ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Cl Transport ◽  
Henle's Loop ◽  
Perfusion Studies

Arginine vasopressin (AVP) has been shown to stimulate active Cl transport across the medullary thick ascending limb of Henle's loop (MAL) in association with an increase in adenylate cyclase activity. To determine whether the failure to demonstrate active Cl transport across the thin ascending limb of Henle's loop (TAL) in previous in vitro perfusion studies was due to the absence of AVP in the preparation, we examined the effect of AVP on adenylate cyclase activity and Cl transport in the hamsters TAL. AVP (1 mU/ml) increased adenylate cyclase activity in the hamster TAL (20.7 +/- 5.2 control vs. 46.2 +/- 10.1 fmol . mm-1 . 30 min-1, n = 6, P less than 0.05) but not in the descending limb (27.8 +/- 7.0 control vs. 20.4 +/- 2.7, n = 4, P less than 0.05). When both MAL and TAL were perfused, a lumen-positive transepithelial voltage (Vt) was observed. The Vt was increased by adding 1 or 10 mU/ml AVP to the bath. When only the TAL was perfused, the Vt was not different from zero. Similar results were obtained in mouse renal tubules. In other experiments, AVP did not affect the diffusion potential generated when a transepithelial NaCl gradient was present. AVP or dibutyryl cAMP caused little or no change in efflux of radioactive chloride across the hamster TAL. These findings suggest that electrogenic chloride transport is not demonstrable in the TAL even in the presence of AVP. The physiologic role of AVP-sensitive adenylate cyclase in the TAL remains to be established.

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.

Dynamics of nucleotides in distal nephron of mice with nephrogenic diabetes insipidus

1986 ◽  
Vol 250 (1) ◽  
pp. F151-F158 ◽  
Author(s):  
E. Kusano ◽  
A. N. Yusufi ◽  
N. Murayama ◽  
J. Braun-Werness ◽  
T. P. Dousa
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Fold Increase ◽  
Thick Ascending Limb ◽  
Camp Phosphodiesterase ◽  
Camp Content ◽  
Medullary Thick Ascending Limb ◽  
Atp Levels ◽  
Collecting Tubules ◽  
Camp Levels

In mice with hereditary nephrogenic diabetes insipidus (NDI), the high activity of cAMP-phosphodiesterase (cAMP-PDIE) in medullary collecting tubules (MCT) prevents the increase in cAMP content in response to vasopressin [Arg8]vasopressin (AVP). Even when the cAMP response to AVP is partly corrected by cAMP-PDIE inhibitor 1-methyl-3-isobutylxanthine (MIX), under all tested conditions the cAMP levels in MCT of NDI mice remained much lower than in controls (B. A. Jackson, R. M. Edwards, H. Valtin, and T. P. Dousa, J. Clin. Invest. 66: 110-122, 1980). In the present study, we explored which factors may account for this defect. We determined contents of ATP, nicotinamide adenine dinucleotide (NAD), and the levels of cAMP in MCT and in medullary thick ascending limb of Henle's loop (MAL) microdissected from control and NDI mice. In the presence of 1 microM AVP and 0.05 mM MIX, the cAMP levels accumulated in MCT of NDI mice were four times lower compared with controls, but the levels of ATP and NAD were not different. ATP levels in MAL of NDI mice were slightly (delta -23%) lower than in MAL from controls, and in distal convoluted tubules (DCT) of NDI mice the ATP levels were also decreased (delta -49%). Although AVP alone had little effect on cAMP levels in mouse MAL in the presence of 0.1 mM forskolin, the AVP elicited a 20-fold increase of cAMP of both the control and NDI mice. Addition of 0.1 mM forskolin further increased the cAMP accumulation in MCT incubated with AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals High-mobility group box 1 inhibits HCO3− absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway

2015 ◽  
Vol 309 (8) ◽  
pp. F720-F730 ◽  
Author(s):  
David W. Good ◽  
Thampi George ◽  
Bruns A. Watts
Keyword(s):  
Advanced Glycation End Products ◽  
Basolateral Membrane ◽  
High Mobility ◽  
High Mobility Group ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Advanced Glycation ◽  
Medullary Thick Ascending Limb ◽  
Glycation End Products ◽  
End Products

High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296–C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO3- absorption through the same pathway. Adding HMGB1 to the bath decreased HCO3− absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4−/− mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO3−absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO3− absorption mediated through Na+/H+ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO3− absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO3− absorption through different receptor signaling pathways.

Potassium adaptation in hypothyroidism: changes in transport adenosinetriphosphatases

1993 ◽  
Vol 264 (1) ◽  
pp. F31-F36 ◽  
Author(s):  
M. M. Salem ◽  
Y. Chen ◽  
S. K. Mujais
Keyword(s):  
Morphological Changes ◽  
Thick Ascending Limb ◽  
Adaptive Responses ◽  
Medullary Thick Ascending Limb ◽  
Potassium Adaptation ◽  
Adenosine Triphosphatases ◽  
Collecting Tubule ◽  
Pump Activity ◽  
Major Increase ◽  
K Depletion

To evaluate whether hypothyroidism alters the adaptive responses of renal transport adenosine-triphosphatases (ATPases) to modifications in dietary K content, we examined the activities of Na-K pump and H-K pump in hypothyroid rats under basal conditions and after dietary K changes. Hypothyroidism led to a decline in Na-K pump activity in all three nephron segments examined [proximal convoluted tubule from 2,333 +/- 103 to 1,099 +/- 32, medullary thick ascending limb from 4,344 +/- 119 to 1,613 +/- 61, and cortical collecting tubule (CCT) from 1,133 +/- 45 to 640 +/- 38 pmol.mm-1 x h-1; all P < 0.01 vs. euthyroid] along with morphological changes manifest in a decrease in tubule diameter. K loading led to an increase in Na-K pump activity in the CCT of both euthyroid (from 1,133 +/- 45 to 2,269 +/- 74, pmol.mm-1 x h-1, P < 0.01) and hypothyroid (from 640 +/- 38 to 1,118 +/- 67 pmol.mm-1 x h-1, P < 0.01) animals. Furthermore, in euthyroid rats, 3 wk of K depletion led to a major increase in H-K pump activity in both the CCT (from 203 +/- 14 to 331 +/- 22 pmol.mm-1 x h-1, P < 0.01) and medullary collecting tubule (MCT, from 137 +/- 9 to 210 +/- 14 pmol.mm-1 x h-1, P < 0.01). Hypothyroidism was associated with a decline in H-K pump activity in the CCT and MCT (to 94 +/- 6 and 55 +/- 5 pmol.mm-1 x h-1, respectively; both P < 0.01 vs. euthyroid).(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of Na+/K+-ATPase activity by polyamines in the rat renal medullary cells of the thick ascending limb of Henle's loop

1990 ◽  
Vol 127 (3) ◽  
pp. 377-382 ◽  
Author(s):  
J. A. Charlton ◽  
P. H. Baylis
Keyword(s):  
Atpase Activity ◽  
Arginine Vasopressin ◽  
Thick Ascending Limb ◽  
Stimulus Response ◽  
Spermine Synthase ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Specific Inhibitors ◽  
Stimulation Of

ABSTRACT Previous studies have indicated that ornithine decarboxylase (ODC) may be involved in the stimulation of Na+/K+-ATPase activity by arginine vasopressin (AVP) in the rat renal medullary thick ascending limb of Henle's loop. The present study was aimed at establishing the role of the polyamines, the conversion products of ODC activity, in the stimulation of Na+/K+-ATPase by AVP. Using cytochemical methods, we have demonstrated an increase in Na+/K+-ATPase activity after stimulation with putrescine, spermidine and spermine (each 1 mmol/l) for 2·5,2 and 1·5 min respectively. The specific inhibitors of spermidine and spermine synthase, bis-cyclohexylammonium sulphate and N-alkylated-1,3-diaminopropane respectively, inhibited the stimulation of Na+/K+-ATPase by AVP, this inhibition being reversed by spermine. These findings suggest that polyamines are involved in the stimulus-response coupling of the hormone-mediated response. Journal of Endocrinology (1990) 127, 377–382

scholarly journals Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat

2012 ◽  
Vol 44 (17) ◽  
pp. 829-842 ◽  
Author(s):  
Nadezhda N. Zheleznova ◽  
Chun Yang ◽  
Robert P. Ryan ◽  
Brian D. Halligan ◽  
Mingyu Liang ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Thick Ascending Limb ◽  
Oxygen Utilization ◽  
Outer Medulla ◽  
High Salt Diet ◽  
Salt Diet ◽  
Medullary Thick Ascending Limb ◽  
False Discovery ◽  
Tissue Homogenates ◽  
Single Cell Type

The renal medullary thick ascending limb (mTAL) of the Dahl salt-sensitive (SS) rat is the site of enhanced NaCl reabsorption and excess superoxide production. In the present studies we isolated mitochondria from mTAL of SS and salt-resistant control strain SS.13BN rats on 0.4 and 8% salt diet for 7 days and performed a proteomic analysis. Purity of mTAL and mitochondria isolations exceeded 93.6 and 55%, respectively. Using LC/MS spectral analysis techniques we identified 96 mitochondrial proteins in four biological mTAL mitochondria samples, run in duplicate, as defined by proteins with a false discovery rate <5% and scan count ≥2. Seven of these 96 proteins, including IDH2, ACADM, SCOT, Hsp60, ATPA, EFTu, and VDAC2 were differentially expressed between the two rat strains. Oxygen consumption and high-resolution respirometry analyses showed that mTAL cells and the mitochondria in the outer medulla of SS rats fed high-salt diet exhibited lower rates of oxygen utilization compared with those from SS.13BN rats. These studies advance the conventional proteomic paradigm of focusing exclusively upon whole tissue homogenates to a focus upon a single cell type and specific subcellular organelle. The results reveal the importance of a largely unexplored role for deficiencies of mTAL mitochondrial metabolism and oxygen utilization in salt-induced hypertension and renal medullary oxidative stress.

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.

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