scholarly journals Prenatal programming of rat proximal tubule Na+/H+ exchanger by dexamethasone

2007 ◽  
Vol 292 (3) ◽  
pp. R1230-R1235 ◽  
Author(s):  
Amit Dagan ◽  
Jyothsna Gattineni ◽  
Vodi Cook ◽  
Michel Baum
Keyword(s):  
Proximal Tubule ◽  
Membrane Vesicles ◽  
Sodium Reabsorption ◽  
Prenatal Programming ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Old Rats ◽  
Convoluted Tubules

Prenatal administration of dexamethasone causes hypertension in rats when they are studied as adults. Although an increase in tubular sodium reabsorption has been postulated to be a factor programming hypertension, this has never been directly demonstrated. The purpose of this study was to examine whether prenatal programming by dexamethasone affected postnatal proximal tubular transport. Pregnant Sprague-Dawley rats were injected with intraperitoneal dexamethasone (0.2 mg/kg) daily for 4 days between the 15th and 18th days of gestation. Prenatal dexamethasone resulted in an elevation in systolic blood pressure when the rats were studied at 7–8 wk of age compared with vehicle-treated controls: 131 ± 3 vs. 115 ± 3 mmHg ( P < 0.001). The rate of proximal convoluted tubule volume absorption, measured using in vitro microperfusion, was 0.61 + 0.07 nl·mm−1·min−1 in control rats and 0.93+ 0.07 nl·mm−1·min−1 in rats that received prenatal dexamethasone ( P < 0.05). Na+/H+ exchanger activity measured in perfused tubules in vitro using the pH-sensitive dye BCECF showed a similar 50% increase in activity in proximal convoluted tubules from rats treated with prenatal dexamethasone. Although there was no change in abundance of NHE3 mRNA, the predominant luminal proximal tubule Na+/H+ exchanger, there was an increase in NHE3 protein abundance on brush-border membrane vesicles in 7- to 8-wk-old rats receiving prenatal dexamethasone. In conclusion, prenatal administration of dexamethasone in rats increases proximal tubule transport when rats are studied at 7–8 wk old, in part by stimulating Na+/H+ exchanger activity. The increase in proximal tubule transport may be a factor mediating the hypertension by prenatal programming with dexamethasone.

Mechanism of prostaglandin E2-induced increase of proximal sodium reabsorption in the rat

1990 ◽  
Vol 258 (1) ◽  
pp. R82-R86 ◽  
Author(s):  
Y. Kinoshita ◽  
F. G. Knox
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Rat Kidney ◽  
Sodium Reabsorption ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Convoluted Tubules ◽  
Stimulation Of ◽  
Interstitial Infusion

Prostaglandin E2, when infused directly into the renal interstitium, enhances sodium reabsorption by the superficial proximal convoluted tubules of anesthetized Sprague-Dawley rats. The present study was designed to investigate the role of angiotensin II in the prostaglandin E2-induced stimulation of proximal sodium reabsorption. Micropuncture at the superficial late proximal tubule demonstrated a significant increase in the fractional reabsorption of sodium from 39.9 +/- 2.3% in control conditions to 51.8 +/- 3.0% (n = 9, P less than 0.01) during the renal interstitial infusion of prostaglandin E2. The stimulatory effect of prostaglandin E2 on proximal sodium reabsorption was markedly attenuated by pretreatment with saralasin. During intravenous saralasin infusion, prostaglandin E2 did not significantly change the fractional reabsorption of sodium from 42.2 +/- 5.8 to 45.4 +/- 6.0% (n = 7, NS). In summary, the stimulatory effect of renal interstitial infusion of prostaglandin E2 on proximal sodium reabsorption was attenuated by pretreatment with saralasin. Therefore renal interstitial infusion of prostaglandin E2 may enhance proximal sodium reabsorption, at least in part, through stimulation of angiotensin II production in the rat kidney.

NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity

2007 ◽  
Vol 293 (1) ◽  
pp. F212-F218 ◽  
Author(s):  
Hetal S. Kocinsky ◽  
Diane W. Dynia ◽  
Tong Wang ◽  
Peter S. Aronson
Keyword(s):  
Cell Model ◽  
Membrane Vesicles ◽  
Sprague Dawley ◽  
Opossum Kidney ◽  
Sprague Dawley Rats ◽  
Sodium Hydrogen Exchanger ◽  
Tightly Coupled ◽  
Type 3

Direct phosphorylation of sodium hydrogen exchanger type 3 (NHE3) is a well-established physiological phenomenon; however, the exact role of NHE3 phosphorylation in its regulation remains unclear. The objective of this study was to evaluate whether NHE3 phosphorylation at serines 552 and 605 is physiologically regulated in vivo and, if so, whether changes in phosphorylation at these sites are tightly coupled to changes in transport activity. To this end, we directly compared PKA-induced NHE3 inhibition with site-specific changes in NHE3 phosphorylation in vivo and in vitro. In vivo, PKA was activated using an intravenous infusion of parathyroid hormone in Sprague-Dawley rats. In vitro, PKA was activated directly in opossum kidney (OKP) cells using forskolin and IBMX. NHE3 activity was assayed in microvillar membrane vesicles in the rat model and by 22Na uptake in the OKP cell model. In both cases, NHE3 phosphorylation at serines 552 and 605 was determined using previously characterized monoclonal phosphospecific antibodies directed to these sites. In vivo, we found dramatic changes in NHE3 phosphorylation at serines 552 and 605 with PKA activation but no corresponding alteration in NHE3 activity. This dissociation between NHE3 phosphorylation and activity was further verified in OKP cells in which phosphorylation clearly preceded transport inhibition. We conclude that although phosphorylation of NHE3 at serines 552 and 605 is regulated by PKA both in vivo and in vitro, phosphorylation of these sites does not directly alter Na+/H+ exchange activity.

scholarly journals Ontogeny of rabbit proximal tubule urea permeability

2001 ◽  
Vol 280 (6) ◽  
pp. R1713-R1718 ◽  
Author(s):  
Raymond Quigley ◽  
Amber Lisec ◽  
Michel Baum
Keyword(s):  
Activation Energy ◽  
Proximal Tubule ◽  
Brush Border Membrane ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Urea Transport ◽  
Urea Permeability ◽  
Convoluted Tubules ◽  
Stop Flow

Urea transport in the proximal tubule is passive and is dependent on the epithelial permeability. The present study examined the maturation of urea permeability (Purea) in in vitro perfused proximal convoluted tubules (PCT) and basolateral membrane vesicles (BLMV) from rabbit renal cortex. Urea transport was lower in neonatal than adult PCT at both 37 and 25°C. The PCT Purea was also lower in the neonates than the adults (37°C: 45.4 ± 10.8 vs. 88.5 ± 15.2 × 10−6 cm/s, P < 0.05; 25°C: 28.5 ± 6.9 vs. 55.3 ± 10.4 × 10−6 cm/s; P < 0.05). The activation energy for PCT Purea was not different between the neonatal and adult groups. BLMV Purea was determined by measuring vesicle shrinkage, due to efflux of urea, using a stop-flow instrument. Neonatal BLMV Purea was not different from adult BLMV Purea at 37°C [1.14 ± 0.05 × 10−6 vs. 1.25 ± 0.05 × 10−6 cm/s; P = not significant (NS)] or 25°C (0.94 ± 0.06 vs. 1.05 ± 0.10 × 10−6 cm/s; P= NS). There was no effect of 250 μM phloretin, an inhibitor of the urea transporter, on Purea in either adult or neonatal BLMV. The activation energy for urea diffusion was also identical in the neonatal and adult BLMV. These findings in the BLMV are in contrast to the brush-border membrane vesicles (BBMV) where we have previously demonstrated that urea transport is lower in the neonate than the adult. Urea transport is lower in the neonatal proximal tubule than the adult. This is due to a lower rate of apical membrane urea transport, whereas basolateral urea transport is the same in neonates and adults. The lower Purea in neonatal proximal tubules may play a role in overall urea excretion and in developing and maintaining a high medullary urea concentration and thus in the ability to concentrate the urine during renal maturation.

Production and functional roles of nitric oxide in the proximal tubule

2000 ◽  
Vol 278 (5) ◽  
pp. R1117-R1124 ◽  
Author(s):  
Mingyu Liang ◽  
Franklyn G. Knox
Keyword(s):  
Nitric Oxide ◽  
Proximal Tubule ◽  
In Vivo Studies ◽  
Sodium Reabsorption ◽  
Functional Roles ◽  
Enhanced Production ◽  
Proximal Tubular ◽  
Final Effect

A significant role for nitric oxide (NO) in proximal tubule physiology and pathophysiology has been revealed by a series of in vivo and in vitro studies. Whether the proximal tubule produces NO under basal conditions is still controversial; however, evidence suggests that the proximal tubule is constantly exposed to NO that might include NO from nonproximal tubule sources. When challenged with a variety of stimuli, including hypoxia, the proximal tubule is able to produce large quantities of NO. In vivo studies generally indicate that NO inhibits fluid and sodium reabsorption by the proximal tubule. However, the final effect of NO on proximal tubular reabsorption appears to depend on the concentration of NO and involve interaction with other regulatory mechanisms. NO regulates Na+-K+-ATPase, Na+/H+ exchangers, and paracellular permeability of proximal tubular cells, which may contribute to its effect on proximal tubular transport. Enhanced production of NO, perhaps depending on macrophage type inducible NO synthase, participates in hypoxic/ischemic proximal tubular injury. In conclusion, NO plays a fundamental role in both physiology and pathophysiology of the proximal tubule.

Light and electron microscopic investigation of adenohypophyses of germfree, food-restricted, and germfree-food restricted aging, male lobund-wistar rats

1988 ◽  
Vol 46 ◽  
pp. 352-353
Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Microscopic Investigation ◽  
Electron Microscopic Investigation ◽  
Aging Male ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Sprague Dawley Rats ◽  
Old Rats ◽  
Ad Libitum ◽  
Microscopic Findings

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

2013 ◽  
Vol 32 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Antoinette Y. Odendaal ◽  
Narendra S. Deshmukh ◽  
Tennille K. Marx ◽  
Alexander G. Schauss ◽  
John R. Endres ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Study ◽  
Developmental Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

2007 ◽  
Vol 292 (2) ◽  
pp. F861-F867 ◽  
Author(s):  
Melvin R. Hayden ◽  
Nazif A. Chowdhury ◽  
Shawna A. Cooper ◽  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Proximal Tubule ◽  
Structural Damage ◽  
Kidney Tissue ◽  
Proximal Tubule Cell ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

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