scholarly journals Cisplatin Decreases the Abundance of Aquaporin Water Channels in Rat Kidney

2001 ◽  
Vol 12 (5) ◽  
pp. 875-882
Author(s):  
SOO-WAN KIM ◽  
JONG-UN LEE ◽  
MYONG-YUN NAH ◽  
DAE-GILL KANG ◽  
KYU-YOUN AHN ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Rat Kidney ◽  
Free Water ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Water Channels ◽  
Control Group ◽  
Urinary Concentration ◽  
Sprague Dawley ◽  
Outer Medulla

Abstract. The present study examined whether the cisplatininduced urinary concentration defect can be related to an altered regulation of aquaporin (AQP) water channels in the kidney. Cisplatin (8 mg/kg) was injected intraperitoneally into male Sprague-Dawley rats. The control group was without cisplatin treatment. Four d later, the expression of AQP1, AQP2, and AQP3 proteins was determined in the kidney. To specify further the primary point of derangement in the pathway that activates the arginine vasopressin—mediated AQP channels, different components of adenylyl cyclase complex were examined separately. The cisplatin treatment caused a polyuric renal failure in association with decreases of free water reabsorption. The expression of AQP1 and AQP2 was decreased in the cortex, the outer medulla, and the inner medulla, whereas that of AQP3 was decreased in the outer medulla and the inner medulla. The expression of AQP2 proteins in the apical membrane-enriched fraction decreased in parallel with that in the subapical vesicle-enriched fraction, indicating a preserved targeting. Immunohistochemistry of the outer medulla also revealed that cisplatin decreased immunoreactivity for AQP1, AQP2, and AQP3. The arginine vasopressin—evoked generation of cyclic adenosine monophosphate was attenuated by cisplatin, being most prominent in the outer medulla. However, the cyclic adenosine monophosphate generation in response to forskolin was not affected, whereas that to sodium fluoride was diminished significantly. Cisplatin also decreased the expression of Gsα proteins in the outer medulla and the inner medulla. These results suggest that a reduced expression of AQP water channels accounts at least in part for the cisplatin-induced urinary concentration defect.

scholarly journals Diminished Renal Expression of Aquaporin Water Channels in Rats with Experimental Bilateral Ureteral Obstruction

2001 ◽  
Vol 12 (10) ◽  
pp. 2019-2028 ◽  
Author(s):  
SOO WAN KIM ◽  
SAM HYEON CHO ◽  
BONG SUK OH ◽  
CHUNG HO YEUM ◽  
KI CHUL CHOI ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Arginine Vasopressin ◽  
Ureteral Obstruction ◽  
Free Water ◽  
Water Channels ◽  
Urinary Flow ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
Camp Generation ◽  
Renal Expression

Abstract. Whether postobstructive diuresis could be related to altered regulation of aquaporin (AQP) water channels in the kidney was investigated. Male Sprague-Dawley rats underwent bilateral obstruction of the proximal ureters for 48 h. The renal expression of AQP1 to AQP4 proteins was then determined by Western blot and immunohistochemical analyses. For elucidation of the primary impairment in the upstream pathway leading to the expression of cAMP-mediated AQP channels, the expression of Gsαand that of adenylyl cyclase were also determined. For some rats, the obstruction was released for collection of urine samples. After the ureteral obstruction, the urinary flow rate was increased and free water reabsorption was decreased. In the obstructed kidneys, the expression of AQP1 to AQP3 was decreased in the cortex, outer medulla, and inner medulla, whereas that of AQP4 was decreased in the inner medulla. Immunoreactivities for AQP1 to AQP4 were also decreased in the obstructed kidneys. The protein expression of Gsαwas decreased in the cortex, outer medulla, and inner medulla, whereas that of adenylyl cyclase VI was decreased in the outer and inner medullae. cAMP generation stimulated by arginine vasopressin was decreased in the cortex, outer medulla, and inner medulla. cAMP generation in response to forskolin was decreased in the outer and inner medullae, whereas that in response to sodium fluoride was decreased in the cortex, outer medulla, and inner medulla. These results suggest that a reduced abundance of AQP water channels in the kidney accounts in part for postobstructive diuresis. The primary impairment of AQP channels that are regulated via the arginine vasopressin/cAMP pathway may lie at the level of G proteins and adenylyl cyclase itself.

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.

168 EFFECT OF CYCLIC ADENOSINE MONOPHOSPHATE MODULATORS DURING OOCYTE IN VITRO MATURATION ON BOVINE EMBRYOS (Gyr×HOLSTEIN) QUALITY

2016 ◽  
Vol 28 (2) ◽  
pp. 214
Author(s):  
G. R. Leal ◽  
C. A. S. Monteiro ◽  
H. F. R. A. Saraiva ◽  
A. J. R. Camargo ◽  
P. M. S. Rosa ◽  
...  
Keyword(s):  
Lipid Content ◽  
In Vitro Maturation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Bovine Embryos ◽  
Tropical Conditions ◽  
Significant Difference ◽  
Number Of Cells

In vitro embryo production (IVP) is an important tool for cattle breeding. Brazilian dairy systems are based on Gyr × Holstein crossbreds, which integrates adaptability to tropical conditions and milk production. Quality determines the oocyte proportion that will develop to blastocyst stage, and although the lipid content is important in oocyte development, a high concentration in embryos is associated with cryotolerance reduction, making this a relevant issue for IVP systems. The in vitro maturation system (IVM) simulated physiological oocyte maturation (SPOM) mimics the physiological maturation events by using cyclic adenosine monophosphate (cAMP) modulators, which promote the increase of oocyte competence. Among the modulators, Forskolin has lipolytic properties. The aim of this study was to evaluate the effect of the SPOM system (Albuz 2010 Hum. Reprod. 25, 12) on bovine embryos (Gyr × Holstein) regarding their total number of cells (TNC) and lipid content. Oocytes were obtained by ovum pick-up from Gyr cows in 5 replications. After selection, they were randomly divided into 2 groups: SPOM (S) and control (C). The IVM lasted 24 h for group C (TCM 199 medium without FBS) in culture oven at 38.5°C, 5% CO2 in atmospheric air and high humidity. In the SPOM system, oocytes were in pre-IVM [TCM 199 medium + 100 µM Forskolin + 500 µM 3-isobutyl-1-methylxanthine (IBMX)] for 2 h and followed for extended IVM (TCM 199 medium + 20 µM cilostamide) for 28 h under the same conditions as control group. After IVM, oocytes were fertilised with semen from a single Holstein bull that was prepared by Percoll gradient method in Fert-TALP medium (Bioklone® Animal Reproduction, São Paulo, Brazil) for 22 h and transfered to culture droplets, where they remained for 7 days (n = 10–13 per group). The lipid content analysis was performed by staining with Oil red and the stained area fraction of each embryo was measured using software ImageJ (NIH, Bethesda, MD, USA). The TNC was measured after being stained with Hoechst 33342 and results were analysed by Student's t-test in Instat GraphPad program, with a 5% significance level. There was no significant difference (P > 0.05) between embryos from both groups on TNC (group S: 88.9 ± 28.0A; group C: 101.6 ± 29.1a) and lipid content (group S: 0.93 ± 12:18A; group C: ±0.15 to 0.96) analysis. Some studies have shown there is a beneficial effect on embryo quality when using this system; however, our results demonstrated that there was no effect on total number of cells using our conditions. Some authors have also demonstrated a reduction in embryo lipid content using Forskolin during in vitro culture. Our results suggest that the time of Forskolin exposure was not enough to ensure lipolytic action on the structures produced from oocytes (Gyr) treated in pre-IVM. It was concluded that the SPOM system had no effect on TNC and lipid content of Gyr/Holstein embryos. Financial support from FAPERJ and CAPES is acknowledged.

239 USE OF CYCLIC ADENOSINE MONOPHOSPHATE MODULATORS IN IN VITRO PRODUCTION OF BOVINE EMBRYOS

2015 ◽  
Vol 27 (1) ◽  
pp. 209
Author(s):  
T. Fanti ◽  
N. M. Ortega ◽  
R. Garaguso ◽  
M. J. Franco ◽  
C. Herrera ◽  
...  
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Basal Medium ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Hatching Rate ◽  
Bovine Embryos ◽  
Oocyte Competence

In vitro embryo production systems (IVP) try to emulate and enhance molecular events that occur in in vivo reproductive systems in order to increase, not only the number of embryos generated, but also their quality. Despite advances, IVP processes are still inefficient compared with in vivo systems. Several studies have attributed this deficiency to a lack of oocyte competence due to spontaneous premature resumption of meiotic maturation in the oocyte following the removal from its follicular environment. Therefore, our objective was to increase oocyte competence avoiding premature resumption of meiosis by using cyclic adenosine monophosphate modulators. Cumulus-oocyte complexes (COC) were obtained from ovaries of slaughterhouses, washed, and randomly allocated in 2 culture systems. Oocytes in the control group (IVM) were cultured for a period of 24 h in basal medium TCM-199 with EGF (1 µg mL–1) supplemented with rhFSH (25 mIU mL–1). Oocytes in the biphasic in vitro maturation (b-IVM) group were cultured for 2 h in a basal medium supplemented with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 500 µM), and an activator of adenylate cyclase (forskolin, 100 µM). Subsequently, COC were washed and cultured in basal medium supplemented with cilostamide (20 µM) and rhFSH (25 mIU mL–1) for 24 h. Maturation rates were analysed and IVF was performed with a dose of 1 × 106 sperm cells mL–1 in IVF-SOF medium. The presumptive zygotes were cultured in continuous-single-culture medium (Irvine) supplemented with 8 mg mL–1 of BSA until they reached the blastocyst stage. No significant differences in maturation, cleavage, and cryotolerance were observed between b-IVM and IVM groups (P > 0.05; Table 1). This study showed that b-IVM produced a significant increase in IVP compared with the control (IVM) at Days 7 and 8 (P < 0.01). Blastocyst hatching rate was significant (P < 0.05) for both treatment and day of analysis. The b-IVM group yielded an increase of 10 and 7.5% at Days 7 and 8, respectively, of IVP. The biphasic maturation showed an improvement in quality regarding the control group, in the timing analysis of production, and hatching percentages, and these results show that the use of cyclic adenosine monophosphate modulators in the oocyte maturation process enhances oocyte competence, which is reflected in increased productivity and embryo quality. We propose this treatment as an alternative to the standard protocols currently used in IVP of bovine embryos. Table 1.Effect of treatment on maturation, cleavage, and cryotolerance

Renal water excretion before and after remission of nephrotic syndrome: Relationship between free water clearance and kidney function, arginine vasopressin, angiotensin II and aldosterone in plasma before and after oral water loading

1986 ◽  
Vol 71 (1) ◽  
pp. 97-104 ◽  
Author(s):  
E. B. Pedersen ◽  
H. Danielsen ◽  
S. S. Sørensen ◽  
B. Jespersen
Keyword(s):  
Nephrotic Syndrome ◽  
Angiotensin Ii ◽  
Arginine Vasopressin ◽  
Free Water ◽  
Control Group ◽  
Ang Ii ◽  
Free Water Clearance ◽  
Water Load ◽  
Control Subjects ◽  
Before And After

1. An oral water load of 20 ml/kg body wt. was given to eight patients with nephrotic syndrome before and after remission of the syndrome, and to 13 healthy control subjects. Urine volume (D), free water clearance (Cwater), plasma concentrations of arginine vasopressin (AVP), angiotensin II (ANG II) and aldosterone (Aldo), were determined before and three times during the first 4 h after loading. 2. D and Cwater increased to a significantly lower level (P < 0.01) after water loading in patients with nephrotic syndrome than in control subjects, but D and Cwater were normal after remission of the syndrome. The maximum increase in Cwater (ΔCwater max.) was 1.07 ml/min (median) before remission and 7.93 ml/min after, compared with 8.01 ml/min in the control group. 3. Creatinine clearance (Ccr) increased significantly after remission (63 ml/min to 88 ml/min, P < 0.01), and the fractional excretion of sodium was enhanced. AVP was higher in the nephrotic syndrome both before (2.9 pmol/l) and after remission (2.9 pmol/l) compared with the control group (1.8 pmol/l). ANG II and Aldo did not change after remission and remained at the same level as in the control group. 4. The elevation in ΔCwatermax after remission was accompanied by an increase in Ccr in all patients and ΔCwatermax. and Ccr were significantly correlated (ρ = 0.600, n = 16, P < 0.05). No relationship was found between the change in ΔCwater max. and ANG II and Aldo. 5. AVP was significantly suppressed in patients with nephrotic syndrome before remission, but not after remission nor in control subjects, so that although AVP did not differ in nephrotic patients before and after remission, AVP cannot be excluded as a contributory factor to the reduction in Cwater in the nephrotic syndrome. 6. It is concluded that patients with nephrotic syndrome excrete an oral water load slower than control subjects and that the excretion rate is normal after remission of the syndrome. It is suggested that the normalization of Cwater may be attributed to an increase in glomerular filtration rate or a decrease in proximal tubular sodium reabsorption, although a possible role for AVP has not been excluded.

scholarly journals Urinary concentrating defect in experimental hemochromatosis.

1996 ◽  
Vol 7 (1) ◽  
pp. 128-134
Author(s):  
X J Zhou ◽  
N D Vaziri ◽  
D Pandian ◽  
Z Q Wang ◽  
M Mazowiecki ◽  
...  
Keyword(s):  
Urine Osmolality ◽  
Control Group ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
Tubular Atrophy ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Urinary Concentrating Ability ◽  
Convoluted Tubules ◽  
Concentrating Defect

We studied the urinary concentrating capacity in experimental hemochromatosis. Sprague-Dawley rats were randomized into iron (Fe)-loaded (injected sc with 1.2 g elemental iron/kg body weight as iron dextran) and pair-fed control groups. The urinary concentrating ability was studied after 10 months of iron loading. At basal condition, urine osmolality (Uosm) was significantly lower (P < 0.05) in the Fe-loaded rats compared with the control animals despite comparable urinary arginine-vasopressin (AVP) excretion in the two groups. Although 48-h water deprivation resulted in comparable rises in plasma concentration and urinary excretion of AVP in the two groups, maximal Uosm in the Fe-loaded animals was significantly lower than that seen in the control group (P < 0.01). Moreover, the observed urinary concentrating defect could not be corrected by pharmacological doses of exogenous AVP. There was no significant difference in renal chloride, sodium, calcium, or magnesium handling at either basal or sodium depleted states. Histologic studies showed marked iron deposition in the cortex and outer medulla accompanied by mild tubular atrophy particularly in the distal convoluted tubules. Thus, chronic experimental iron overload leads to nephrogenic diabetes insipidus marked by AVP-resistant urinary concentrating defect.

Neuroretinal Dysfunction in Patients Affected by Neurofibromatosis Type 1

2021 ◽  
Author(s):  
Antonietta Moramarco ◽  
Luca Lucchino ◽  
Fabiana Mallone ◽  
Michela Marcelli ◽  
Ludovico Alisi ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Healthy Subjects ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Neurofibromatosis Type ◽  
Implicit Time ◽  
Control Group ◽  
Ophthalmological Examination ◽  
Significant Difference

Abstract The aim of the study was to examine neuroretinal function by using the mfERG test in patients with neurofibromatosis type 1 (NF1) without optic pathway gliomas (OPGs). This study was conducted on 35 patients (35 eyes) with NF1 and 30 healthy subjects (30 eyes) for the control group. Each subject underwent a complete ophthalmological examination including multifocal electroretinography (mfERG). 1.5-Tesla magnetic resonance imaging (MRI) scan of the brain was performed in NF1 patients to assess the presence of OPGs. All participants were recruited having a best corrected visual acuity (BCVA) of no less than 20/20 in each eye. The amplitude and implicit time of the P1 wave (first-order Kernel component) were evaluated on mfERG. Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field. Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy subjects, while the reduction was not significant in the 2 central degrees. A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group, with lower amplitudes in the nasal quadrants. No differences in the implicit times were recorded in the 4 quadrants and in the 2 central degrees as compared between NF1 patients and controls. The present study demonstrates impaired neuroretinal function in NF1 patients. Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate (cAMP) generation, could be involved. Our results suggest a possible use of mfERG as subclinical retinal damage indicator with a potential utility in clinical practice for the follow-up of NF1 patients.

scholarly journals Thyroxin Protects White Matter from Hypoxic-Ischemic Insult in the Immature Sprague–Dawley Rat Brain by Regulating Periventricular White Matter and Cortex BDNF and CREB Pathways

2018 ◽  
Vol 19 (9) ◽  
pp. 2573 ◽  
Author(s):  
Pi-Lien Hung ◽  
Mei-Hsin Hsu ◽  
Hong-Ren Yu ◽  
Kay L. H. Wu ◽  
Feng-Sheng Wang
Keyword(s):  
White Matter ◽  
Growth Factor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Periventricular White Matter ◽  
Sprague Dawley ◽  
Immature Brain ◽  
Artery Ligation ◽  
Chain Reactions ◽  
Amino Terminal

Background: Periventricular white-matter (WM) injury is a prominent feature of brain injury in preterm infants. Thyroxin (T4) treatment reduces the severity of hypoxic-ischemic (HI)-mediated WM injury in the immature brain. This study aimed to delineate molecular events underlying T4 protection following periventricular WM injury in HI rats. Methods: Right common-carotid-artery ligation, followed by hypoxia, was performed on seven-day-old rat pups. The HI pups were injected with saline, or 0.2 or 1 mg/kg of T4 at 48–96 h postoperatively. Cortex and periventricular WM were dissected for real-time (RT)-quantitative polymerase chain reactions (PCRs), immunoblotting, and for immunofluorescence analysis of neurotrophins, myelin, oligodendrocyte precursors, and neointimal. Results: T4 significantly mitigated hypomyelination and oligodendrocyte death in HI pups, whereas angiogenesis of periventricular WM, observed using antiendothelium cell antibody (RECA-1) immunofluorescence and vascular endothelium growth factor (VEGF) immunoblotting, was not affected. T4 also increased the brain-derived neurotrophic factors (BDNFs), but not the nerve growth factor (NGF) expression of injured periventricular WM. However, phosphorylated extracellular signal regulated kinase (p-ERK) and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) concentrations, but not the BDNF downstream pathway kinases, p38, c-Jun amino-terminal kinase (c-JNK), or Akt, were reduced in periventricular WM with T4 treatment. Notably, T4 administration significantly increased BDNF and phosphorylated CREB in the overlying cortex of the HI-induced injured cortex. Conclusion: Our findings reveal that T4 reversed BNDF signaling to attenuate HI-induced WM injury by activating ERK and CREB pathways in the cortex, but not directly in periventricular WM. This study offers molecular insight into the neuroprotective actions of T4 in HI-mediated WM injury in the immature brain.

RADIOIMMUNOASSAY OF [8-ARGININE]-VASOPRESSIN

1975 ◽  
Vol 80 (3) ◽  
pp. 453-464 ◽  
Author(s):  
U. Merkelbach ◽  
P. Czernichow ◽  
R. C. Gaillard ◽  
M. B. Vallotton
Keyword(s):  
Arginine Vasopressin ◽  
Excretion Rate ◽  
Regression Line ◽  
Plasma Osmolality ◽  
Free Water ◽  
Bartter Syndrome ◽  
Total Output ◽  
Urinary Concentration ◽  
Free Water Clearance ◽  
Significant Difference

ABSTRACT A radioimmunoassay for [8-arginine]-vasopressin (AVP), previously described (Czernichow et al. 1975) has been used for the determination of antidiuretic hormone in a 4 ml urine sample. AVP is extracted from acidified urine with a cation exchanger (Amberlite CG 50) with an overall recovery of 72 %. The blank value measured in extracted samples of urine was 0.29 pg/ml ± 0.21 (sem) and calculated by extrapolation of the regression line of the recovery experiment was 0.49 pg/ml. The coefficient of variation within-assay was 13 % and between-assay 18%. Addition of the amounts of AVP found in each specimen of urine voided gave results nearly identical to those of the amounts found in 24 h pool of urine, indicating that the assay was not affected by changes in concentration of the other urinary components during the day. The daily urinary excretion of AVP measured in 34 subjects was found to be 34 ng in 17 women and 70 ng in 17 men, a significant difference. Urinary concentration and excretion rate of AVP rose during thirst test and during Carter-Robbins test performed in 13 healthy subjects. In the latter test it was observed that the women displayed a strikingly more pronounced AVP elevation after the osmolar stimulus than the men. In both sexes a significant correlation was found between AVP excretion rate and plasma osmolality as well as free water clearance. Three cases of complete or incomplete diabetes insipidus and potomania could be clearly differentiated according to the total output of AVP during the thirst test. Extremely high values of AVP were found in the urine of 5 subjects with Schwartz-Bartter syndrome associated with bronchogenic tumours.

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