Prostanoid synthesis by isolated rat glomeruli: Effect of oestrous cycle and pregnancy

1987 ◽  
Vol 73 (6) ◽  
pp. 641-644 ◽  
Author(s):  
I. Gregoire ◽  
J. P. Dupouy ◽  
P. Fievet ◽  
J. D. Sraer ◽  
A. Fournier
Keyword(s):  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Thromboxane A2 ◽  
Experimental Models ◽  
Oestrous Cycle ◽  
Pregnant Rats ◽  
Threefold Increase ◽  
Pregnant State ◽  
Isolated Rat ◽  
Prostanoid Synthesis

1. An increase in glomerular prostaglandin (PG) synthesis has been reported in two experimental models of increased glomerular filtration rate (GFR). 2. Because pregnancy, in women and rats, is also associated with an increased GFR, we studied PG biosynthesis by glomeruli isolated from pregnant rats in comparison with virgin rats at the different phases of the oestrous cycle. 3. PGE2 and PGF2α synthesis markedly increased during pregnancy (at day 21 of gestation a five- to sevenfold increase of PGE2 and PGF2α was seen; at day 15 of gestation a threefold increase of PGE2 and a sixfold increase of PGF2α was noted). However, thromboxane A2 (TXA2) synthesis was similar in all the groups studied. 4. Among the four phases of the oestrous cycle, dioestrus was characterized by a significant increase in glomerular synthesis of PGE2. 5. The fact that during pregnancy the increase in the vasodilator PGE2 is not counteracted by an increase in the constrictor TXA2 must be taken into account when explaining the glomerular hyperfiltration which characterizes the pregnant state. 6. The increase of PGE2 synthesis during dioestrus should be considered in studies of PG synthesis using virgin rats as controls.

scholarly journals Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

2015 ◽  
Vol 308 (5) ◽  
pp. F411-F419 ◽  
Author(s):  
German Lozano ◽  
Ayah Elmaghrabi ◽  
Jordan Salley ◽  
Khurrum Siddique ◽  
Jyothsna Gattineni ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Control Group ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Mature Adult ◽  
Low Protein

The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group ( P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing.

Effect of perfusate phosphate concentration on responses to PTH in isolated rat kidney

1984 ◽  
Vol 246 (6) ◽  
pp. F907-F915
Author(s):  
S. J. Scheinman ◽  
R. Coulson
Keyword(s):  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Phosphate Concentration ◽  
Electrolyte Excretion ◽  
Clearance Ratio ◽  
Magnesium Excretion ◽  
20 Nm ◽  
Sodium Clearance ◽  
Isolated Rat

We studied the excretion of electrolytes and adenosine 3',5'-cyclic monophosphate (cAMP) by rat kidneys perfused for 2 or 3 h at several concentrations of phosphate (Pi). Fractional phosphate excretion increased with higher perfusate Pi concentrations (up to 4.0 mM Pi) without parathyroid hormone (PTH), but no tubular maximum for phosphate reabsorption was reached. The addition of synthetic bovine 1-34 PTH (bPTH) gave a dose-related phosphaturia that depended on the perfusate Pi level. The urinary cAMP response to doses of bPTH was highly dependent on perfusate Pi concentration: with 20 nM bPTH, urinary cAMP was 211 +/- 94 pmol/ml glomerular filtration rate at 1.2 mM Pi and was 3,998 +/- 711 at 4.0 mM Pi (P less than 0.001). Without bPTH, cAMP excretion did not differ among Pi levels. Calcium-to-sodium clearance ratio rose with time in kidneys perfused without bPTH but fell with the addition of as little as 0.02 nM bPTH, regardless of Pi concentration. Variations in Pi or bPTH did not affect fractional magnesium excretion, which fell by 68% through 3 h of perfusion (P less than 0.001). These data suggest that the effects of Pi concentration on renal electrolyte excretion are consistent with changes in the filtered Pi load but that extracellular Pi concentrations dramatically alter the renal cAMP response to bPTH in the isolated perfused kidney.

Angiotensin II binding to renal glomeruli from sodium-loaded and sodium-depleted rats

1976 ◽  
Vol 230 (5) ◽  
pp. 1187-1193 ◽  
Author(s):  
M Beaufils ◽  
J Sraer ◽  
C Lepreux ◽  
R Ardaillou
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Dissociation Constants ◽  
Sodium Balance ◽  
Renal Glomeruli ◽  
Receptor Sites ◽  
Specificity Of Binding ◽  
Isolated Rat

125I-labeled angiotensin II (125I-labeled AII) and [3H]angiotensin II ([3H]AII) bind specifically to isolated rat glomeruli. Three groups of receptor sites could be defined by the KD value (7.1 +/- 0.3 X 10(-11, 3.4 +/- 0.2 X 10(-10), and 1.6 X 10(-9) M, respectively) and the number of receptor sites (11.6 +/- 1.2, 29.4 +/- 3.9, and 113.8 +/- 3.8 fmol/mg glomerular protein, respectively). Both association and dissociation constants for 125I-labeled AII were greater than those for [3H]AII, but their ratio (KD) remained unchanged. Specificity of binding to these three groups of receptor sites was demonstrated by the following: 1) inhibition of binding of labeled AII by unlabeled hormone or by antagonists; and 2) reversibility of binding, independent of either hormone or receptor degradation. Binding was increased in glomerular preparations from acutely and chronically sodium-loaded rats, compared with glomerular preparations from acutely and chronically sodium-depleted rats. This change in binding resulted from both a change in the number of receptor sites and modification of the affinity of AII for its receptors. KD was higher in preparations from sodium-depleted rats (12.9 +/- 3.3 and 14.6 +/- 3.9 X 10(-11) M in chronically and acutely depleted rats, respectively) than in those from sodium-loaded rats (2.7 +/- 0.2 and 3.9 +/- 1 X 10(-11) M in chronically and acutely sodium-loaded rats, respectively). Changes in the binding of AII to its glomerular receptors could play a role in the adaptation of glomerular filtration rate to the sodium balance.

scholarly journals Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules

2001 ◽  
Vol 281 (1) ◽  
pp. F103-F113 ◽  
Author(s):  
Maria Ohlson ◽  
Jenny Sörensson ◽  
Karin Lindström ◽  
Anna M. Blom ◽  
Erik Fries ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Hydrostatic Pressure ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Pore Analysis ◽  
Fivefold Increase ◽  
Different Shapes ◽  
Glomerular Barrier ◽  
Isolated Rat ◽  
Rat Kidneys

The effect of shape on the transglomerular passage of solutes has not been hitherto systematically studied. We perfused isolated rat kidneys to determine the fractional clearances (θ) at various filtration rates for four molecules of different shapes but with similar Stokes-Einstein radii ( aSE= 34–36 Å). The θ for hyaluronan, bikunin, and Ficoll36 Åwere 66, 16, and 11%, respectively, at a glomerular filtration rate (GFR) of 0.07 ml · min−1· g wet wt−1and decreased to 46, 14, and 7%, respectively, on a fivefold increase in GFR. Under the same conditions, θ for albumin increased from 0.15 to 0.74%, and similar behavior was observed for larger Ficolls ( aSE>45 Å). Pore analysis showed that the “apparent neutral” solute radii of Ficoll, albumin, bikunin, and hyaluronan were 35, 64, 33, and 24 Å, respectively, despite similar aSE. In addition, the properties of the glomerular filter changed with increasing GFR and hydrostatic pressure. We conclude that elongated shape, irrespective of size and charge, drastically increases the transglomerular passage of a solute, an effect that is related to its frictional ratio.

Potassium load prevents the decrease of GFR induced by captopril in sodium-depleted rats

1990 ◽  
Vol 258 (3) ◽  
pp. F670-F674
Author(s):  
M. Rathaus ◽  
A. Pomeranz ◽  
E. Podjarny ◽  
J. Bernheim
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Plasma Aldosterone ◽  
Urinary Kallikrein ◽  
Prostanoid Production ◽  
Na Depletion ◽  
Prostanoid Synthesis ◽  
Stimulation Of

Captopril decreases the glomerular filtration rate (GFR) in Na-depleted rats and inhibits the stimulation of glomerular prostanoid synthesis induced by Na depletion. Because K loading stimulates glomerular prostanoid production in normal rats, we studied the effects of K loading in Na-depleted captopril-treated (LNC) rats. Potassium, but not Cl, loading stimulated the glomerular synthesis of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TxB2). Urinary kallikrein-like activity (UKALLV) and plasma aldosterone increased in K-loaded animals. LNC rats had lower clearances of inulin (CIN) and p-aminohippurate (CPAH) than controls (0.22 +/- 0.02 vs. 0.94 +/- 0.07 and 0.56 +/- 0.12 vs. 2.23 +/- 0.23 ml.min-1.100 g body wt-1, both P less than 0.01). KCl-loaded LNC rats had CIN and CPAH greater than LNC (0.64 +/- 0.16 and 1.90 +/- 0.28 ml.min-1.100 g body wt-1, P less than 0.01). Similar results were observed in LNC rats loaded with a K solution not containing Cl, but not in LNC rats loaded with a mixture of CaCl2, MgCl2, and HCl. In KCl-loaded LNC rats, cyclooxygenase inhibition decreased CIN from 0.49 +/- 0.09 to 0.30 +/- 0.08 ml.min-1.100 g body wt-1 (P less than 0.01). Aprotinin did not affect renal function despite significant decrease of UKALLV. We conclude that K loading prevents the decrease of GFR induced by captopril in Na-depleted rats and that this might be mediated by stimulation of glomerular prostanoid synthesis.

Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

1997 ◽  
Vol 38 (5) ◽  
pp. 690-699 ◽  
Author(s):  
S. O. Hustvedt ◽  
D. Grant ◽  
T. E. Southon ◽  
K. Zech
Keyword(s):  
Glomerular Filtration Rate ◽  
Mr Imaging ◽  
Filtration Rate ◽  
Plasma Clearance ◽  
Extracellular Fluid ◽  
Transplacental Passage ◽  
Pregnant Rats ◽  
Elimination Half ◽  
Foetal Liver ◽  
Plasma Pharmacokinetics

Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14C-MnDPDP or 54MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moiety is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moiety is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. Conclusion: The ligand does not appear to facilitate the transport of Mn into any organ except the kidney for subsequent excretion, and it reduces distribution to the heart. The Mn is taken up by those organs indicated for MR imaging, primarily liver and pan-creas.

Impaired Renal Function in Obstructive Jaundice: Enhanced Glomerular Thromboxane Synthesis and Effects of Thromboxane Receptor Blockade in Bile Duct-Ligated Rats

1995 ◽  
Vol 88 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Herbert J. Kramer ◽  
Kriemhild Schwarting ◽  
Angela Bäcker
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Bile Duct ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Bile Duct Ligation ◽  
Urine Volume ◽  
Thromboxane A2 ◽  
H2 Receptor Antagonist ◽  
Duct Ligation

1. Patients with obstructive jaundice are especially susceptible to acute renal failure. We have previously observed that in rats with bile duct ligation impaired renal function is associated with increased urinary thromboxane excretion. 2. In the present study we therefore investigated, in rats with bile duct ligation, renal function, urinary thromboxane excretion and thromboxane B2 synthesis by isolated glomeruli as well as the effects of the thromboxane A2/prostaglandin H2 receptor antagonist Daltroban on renal function in rats with bile duct ligation as compared with sham-operated rats. 3. On the fourth day after bile duct ligation (n = 7 rats) endogenous creatinine clearance as an estimate of glomerular filtration rate was significantly reduced to 0.74 ± 0.05 (SEM) as compared with 1.06 ± 0.09 ml min−1 g−1 kidney weight in sham-operated rats (n = 7, P < 0.01). In rats with bile duct ligation, urine volume was slightly increased, whereas urinary sodium (Na+) (P < 0.001) and potassium (K+) (P < 0.01) excretion as well as urine osmolarity (P < 0.05) were significantly reduced and lower than in sham-operated rats. 4. Urinary thromboxane excretion was significantly higher in rats with bile duct ligation than in sham-operated rats: 116.6 ± 22.3 versus 56.8 ± 10.2 pmol 24h−1 100 g−1 body weight (P < 0.05). Thromboxane B2 synthesis in glomeruli isolated from rats with bile duct ligation was also significantly higher than in sham-operated rats: 12.6 ± 2.0 versus 6.4 ± 0.9 pmol h−1 mg−1 protein (P < 0.05). 5. The thromboxane A2/prostaglandin H2 receptor antagonist Daltroban normalized glomerular filtration rate in a second group of rats with bile duct ligation (n = 7) to 1.03 ± 0.08 (P < 0.01) and slightly increased it in sham-operated rats (n = 7) to 1.24 ± 0.11 ml min−1 g−1 kidney weight (not significant). Daltroban, while without effects on urine volume and osmolarity in sham-operated rats, further increased urine volume and decreased osmolarity in rats with bile duct ligation after surgery. After surgery Daltroban reduced fractional Na+ and K+ excretion in sham-operated rats and in rats with bile duct ligation. 6. The results suggest that obstructive jaundice following bile duct ligation is associated with enhanced renal glomerular thromboxane A2 synthesis, which suppresses glomerular filtration rate and predisposes to acute renal failure. Treatment with Daltroban, a specific thromboxane A2/prostaglandin H2 receptor antagonist, restores glomerular filtration rate to normal, probably secondary to normalization of disturbed intrarenal blood flow following bile duct ligation.

Maintenance of endothelin-induced renal arteriolar constriction in rats is cyclooxygenase dependent

1993 ◽  
Vol 264 (4) ◽  
pp. F637-F644 ◽  
Author(s):  
K. A. Munger ◽  
K. Takahashi ◽  
M. Awazu ◽  
M. Frazer ◽  
S. A. Falk ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Strong Evidence ◽  
Filtration Rate ◽  
Thromboxane A2 ◽  
Hydraulic Pressure ◽  
Maximal Contraction ◽  
Renal Vasoconstriction ◽  
Arteriolar Resistance ◽  
Selective Increase

Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effects on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not afferent arteriolar resistance, leading to a dramatic increase in transcapillary hydraulic pressure difference. Glomerular filtration rate (GFR), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition, but not during selective thromboxane A2 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10(-6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR.

Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

2015 ◽  
Vol 309 (4) ◽  
pp. F332-F340 ◽  
Author(s):  
Katharina Mederle ◽  
Manuel Meurer ◽  
Hayo Castrop ◽  
Klaus Höcherl
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Kidney Injury ◽  
Thromboxane A2 ◽  
Thrombocyte Count ◽  
Tissue Levels ◽  
Cox 2 ◽  
The Impact ◽  
Cox 1

Thromboxane (Tx) A2 has been suggested to be involved in the development of sepsis-induced acute kidney injury (AKI). Therefore, we investigated the impact of cyclooxygenase (COX)-1 and COX-2 activity on lipopolysaccharide (LPS)-induced renal TxA2 formation, and on endotoxemia-induced AKI in mice. Injection of LPS (3 mg/kg ip) decreased glomerular filtration rate (GFR) and the amount of thrombocytes to ∼50% of basal values after 4 h. Plasma and renocortical tissue levels of TxB2 were increased ∼10- and 1.7-fold in response to LPS, respectively. The COX-1 inhibitor SC-560 attenuated the LPS-induced fall in GFR and in platelet count to ∼75% of basal levels. Furthermore, SC-560 abolished the increase in plasma and renocortical tissue levels of TxB2 in response to LPS. The COX-2 inhibitor SC-236 further enhanced the LPS-induced decrease in GFR to ∼40% of basal values. SC-236 did not alter thrombocyte levels nor the LPS-induced increase in plasma and renocortical tissue levels of TxB2. Pretreatment with clopidogrel inhibited the LPS-induced drop in thrombocyte count, but did not attenuate the LPS-induced decrease in GFR and the increase in plasma TxB2 levels. This study demonstrates that endotoxemia-induced TxA2 formation depends on the activity of COX-1. Our study further indicates that the COX-1 inhibitor SC-560 has a protective effect on the decrease in renal function in response to endotoxin. Therefore, our data support a role for TxA2 in the development of AKI in response to LPS.

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