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R Ardaillou

Publications and source records attributed to R Ardaillou.

At least 163 records · Page 9Linked to original sources
PubMed1983

PGE2 binding sites and PG-stimulated cyclic AMP accumulation in rat isolated glomeruli and glomerular cultured cells.

[3H]PGE2 specifically bound to isolated glomeruli. The KD value and the number of sites were 80 nM and 528 fmoles/mg respectively. PGE1 and PGE2 resulted in equipotent inhibition of binding whereas PGI2 was markedly less active. It was not possible to demonstrate specific receptors for PGE2 in glomerular mesangial and epithelial cultured cells. PGE1, PGE2 and PGI2 (0.1-100 microM) stimulated cyclic AMP concentration both in isolated glomeruli and glomerular cultured cells. Basal cyclic AMP in epithelial cells was greater than in mesangial cells or glomeruli. The cyclic AMP accumulation in the presence of PGs was greatest in mesangial cells. Maximum stimulation was in the range 300-1400%. For the three preparations, PGE2 and PGE1 produced a greater effect than PGI2. ED50 values were identical for PGE1 and PGE2 (5 microM for epithelial cells and glomeruli, 20 microM for mesangial cells). ED50 value for PGI2 were lower than those for PGE1 or PGE2 (0.2, 2 and 5 microM for glomeruli, epithelial cells and mesangial cells, respectively). The effects of the three PGs were not additive when tested at maximally effective concentrations. These results demonstrate that PGE1, PGE2 and PGI2 stimulate glomerular and cellular cyclic AMP. A relationship between [3H]PGE2 binding sites and this biological effect has not been established. The physiological events secondary to the increase in glomerular cyclic AMP are also yet to be determined.

Animals↗
PubMed1983

Response of adenylate cyclase to parathyroid hormone and prostaglandins by human isolated glomeruli.

A role for hormonal substances and other biochemical messengers in the regulation of the glomerular filtration rate has been inferred from the results of micropuncture studies in the rat and from the demonstration of hormone-responsive adenylate cyclase activity in glomeruli isolated from the renal cortex of rats and rabbits. To investigate whether such hormonal factors may contribute to the regulation of glomerular function in humans, we studied the response of adenylate cyclase activity to the administration of human PTH-(1-34) and prostaglandins (PG) by glomeruli isolated from the renal cortex of four human kidneys. PTH and PGs (PGE2, PGI2, and, to a lesser extent, PGF2 alpha) stimulated human glomerular adenylate cyclase activity. Basal adenylate cyclase activity ranged from 0.2-1.2 nmol 20 min-1 mg-1. For each agonist, the percent increase above basal values (at the maximum concentration tested) and the concentration of the agonist that elicited 50% of the maximum stimulation (ED50) were as follows: for PTH 300-460% (10,000 mIU/ml); ED50, 100-550 mIU/ml; for PGE2, 160-380% (10 microM); ED50, 0.4-1.6 microM; and for PGI2, 180-650% (10 microM); ED50, 0.09-0.46 microM. The synthetic guanylnucleotide 5'-guanylylimidodiphosphate [Gpp(NH)p] potentiated the effect of PTH and PGI2, since the combined effects were greater than the sums of the effects of the individual agonists, and there was a significant interaction between Gpp(NH)p and PTH or PGI2, as indicated by three-factor analysis of variance. Additivity, but not potentiation, was observed for PGE2. The effects of PTH plus PGE2 or PGI2 were also additive, a finding that suggests that PTH and PGs are not linked to the same pool of adenylate cyclase. In contrast, the combination of PGE2 and PGI2 resulted in a significantly lower effect than the sum of their individual effects, a finding indicating that these PGs share in part a common pool of adenylate cyclase. Demonstration of PTH- and PG-dependent adenylate cyclase activity in human isolated glomeruli suggests a role for these agonists in the regulation of the glomerular filtration rate in man.

Adenylyl Cyclases↗
PubMed1982

[Protective effect of procyanidolic oligomers on the heterologous phase of glomerulonephritis induced by anti-glomerular basement membrane antibodies].

Treatment by procyanidolic oligomers can significantly decrease the proteinuria indiced in the Rat by intravenous injection of anti glomerular basement membranes antibodies. Immunohistological analysis shows that procyanidolic oligomers do not interfere with the mechanisms of immunopathological injury involved in this model (antibody binding to glomerular basement membrane, complement activation, glomerular influx of polymorphonuclear leucocytes). Their protective effect may be due to an increased resistance of the glomerular capillary to the inflammatory mediators released by neutrophils.

Animals↗
PubMed1982

Histamine H2 receptors in rat renal glomeruli.

The aim of this study was to demonstrate histamine-H2 receptors in glomeruli isolated from rat renal cortex and to correlate binding to stimulation by histamine of glomerular cyclic AMP concentration. Binding studies were performed at 10-12 degrees C using [3H]cimetidine as a tracer. Specificity of binding relies on the following: inhibition of [3H]cimetidine binding by the unlabelled drug, other H2-antagonists and agonists in contrast with the very weak inhibitory effects of H1 agonists and antagonists; reversibility of steady-state binding after addition of unlabelled drug; half inhibition of the glomerular cyclic AMP response to histamine at concentrations of cimetidine close to the KD value derived from the binding studies (3 microM); calculated KD value in agreement with the therapeutical concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding strikingly increased in the presence of copper chloride (20-300 microM) due to an increase both in number of sites and affinity. However this greater binding did not influence either the inhibitory effect of cimetidine on histamine-induced glomerular cyclic AMP concentration or the stimulatory effect of histamine itself. [3H]Cimetidine binding was temperature-dependent since it progressively diminished from 0 to 37 degrees. This was not due to [3H]cimetidine degradation as shown by thin layer chromatography but rather to a change in drug-receptor interaction at higher temperatures. Glumerular concentration of cyclic AMP increased progressively in the presence of histamine (0.1-1000 microM). This stimulatory effect was markedly inhibited by H2 antagonists. These data demonstrate the presence in rat glomeruli of H2 receptors linked to adenylate cyclase.

Animals↗
PubMed1982

In vitro prostaglandin synthesis by various rat renal preparations.

Prostaglandin synthesis by eight different structures from the rat kidney (while cortex, cortical tubules, glomeruli, outer medulla, papilla, glomerular cultured epithelial and mesangial cells, cultured interstitial medullary cells) was measured in vitro after incubation with [14C] arachidonic acid using high-performance liquid chromatography followed by RIA with four specific anti-prostaglandin antibodies (prostaglandin E2, prostaglandin F2 alpha, 6 keto-prostaglandin F1 alpha, thromboxane B2). Prostaglandin production by the whole cortex and cortical tubules was very low. The order of abundance for isolated glomeruli was thromboxane B2 great than prostaglandin E2 greater than prostaglandin F2 alpha greater than 6 keto-prostaglandin F1 alpha. Mesangial cells synthesized prostaglandin E2 at a markedly high rate, in decreasing order: prostaglandin F2 alpha, thromboxane B2 and 6 keto-prostaglandin F1 alpha. The same order of abundance was observed for epithelial cells. The papilla synthesized essentially prostaglandin E2 and prostaglandin F2 alpha, whereas the main product for the outer medullar was 6 keto-prostaglandin F1 alpha. Cultured interstitial cells synthesized mainly prostaglandin E2 and to a lesser extent prostaglandin F2 alpha. Unidentified peaks eluting between 6 keto-prostaglandin F1 alpha and thromboxane B2 were also observed chiefly with glomeruli but they were absent with the medullary preparations. They disappeared after incubation with indomethacin or aspirin and represented for glomeruli the greatest percentage of conversion of [14C] arachidonic acid. These results show that the prostanoid profile varies markedly with the different regions and cells of the rat kidney.

Animals↗
PubMed1982

In vitro prostaglandin synthesis by human glomeruli and papillae.

We have investigated in vitro prostaglandin synthesis by human isolated glomeruli and papillary homogenates and compared the results with those obtained in parallel studies using rat material. Prostaglandins were measured by two methods, namely radiometric high performance liquid chromatography after incubation with 14C arachidonic acid and radioimmunoassay. The relative abundance of various prostaglandins synthesized by glomeruli was different in man (6 keto PGF1 alpha greater than TXB2 greater than PGF2 alpha greater than PGE2) and in the rat (PGE2 greater than or equal to PGF2 alpha greater than TXB2 greater than 6 keto PGF1 alpha). Unidentified peaks eluting between 6 keto PGF1 alpha and TXB2 were observed only in rat glomeruli. These peaks were suppressed by indomethacin. Direct radioimmunoassay of prostaglandins in the incubation medium of human glomeruli confirmed the predominance of 6 keto PGF1 alpha synthesis and showed its stimulation by arachidonic acid, its progressive decrease with time and its linear relationship with glomerular protein at low concentrations. On the contrary, the profile of prostaglandin synthesis by the papilla was similar in man and in the rat, PGE2 and PGF2 alpha being the major products in both species. However, related to one mg of protein, papillary synthesis of these two prostaglandins was greater in the rat. These results show that PGI2 is the major prostaglandin synthesized in human glomeruli and suggest a role for this prostaglandin in glomerular physiology in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Endogenous dopamine synthesis and dopa-decarboxylase activity in rat renal cortex.

The dopamine content of either cortical slices or isolated glomeruli prepared from rat kidneys and of their incubation medium was measured at different times both under basal conditions and in the presence of L-DOPA. Production of dopamine from L-DOPA by purified cytosolic proteins of the whole cortex was also measured. Dopamine synthesized by these 3 renal preparations accumulated linearly with time over 60 min. Dopamine produced by the glomeruli was more rapidly released into the incubation medium than that produced by the cortical slices. The dopamine synthetic rate was very low in the absence of L-DOPA but increased rapidly when L-DOPA was added to the incubation medium. No plateau was reached in the range of concentrations studied (0-100 microM) when cortical slices or cytosolic proteins were studied whereas dopamine production by isolated glomeruli reached an equilibrium above 10 microM L-DOPA. Dopamine synthesis in the presence of 100 microM L-DOPA was linearly related to the amount of renal protein. The synthetic rates were 43, 2.2 and 0.2 nmoles . h-1 . mg -1 for the cytosolic proteins, the cortical slices and the isolated glomeruli respectively. Dopamine synthesis by the cortical slices in the presence of 100 microM L-DOPA was progressively inhibited by increasing concentrations of alpha-methyl-DOPA. Cortical slices prepared from rats treated by benserazide, an inhibitor of L-DOPA decarboxylase, synthesized much less dopamine than those from control rats. These results show that rat renal cortex deprived of neuronal supply can synthesize dopamine in vitro from extracellular L-DOPA.

Animals↗
PubMed1982

Metabolic clearance rate of immunoreactive vasopressin in man.

Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 micrograms AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287.1 ml min-1 (m2)-1 and 219.3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.

Adult↗
PubMed1982

Angiotensin II receptors in human isolated renal glomeruli.

125I-Labeled angiotensin II ([125I]A II) binds specifically to glomeruli isolated from human kidneys that were obtained at nephrectomy or early autopsy. Equilibrium was reached after 30 min, and specific binding represented more than 90% of the total binding. Dissociation after dilution with the addition of an excess of unlabeled hormone was more rapid than after dilution alone. The effect increased as a function of the A II concentration. The Scatchard plot derived from saturation experiments was curvilinear, with an upward concavity. Two groups of receptor sites could be defined by the Kd values (0.1 and 2 nM, respectively) and the number of receptor sites (40 and 300 fmol mg glomerular protein-1, respectively). Alternatively, binding could be considered to follow a negative cooperative type of hormone-receptor interaction. [Asn1, Val5]A II, [Asp1,Ile5]A II, [des, Asp1,Ile5]A II, [Sar1, Ala8]A II, and [Sar1, Ile8]A II were all equally effective as competitive inhibitors of [125I]A II binding. Both calcium and magnesium (0.5-5 mM) produced an increase in [125I]A II specific binding, whereas guanylylimidodiphosphate, an analog of GTP, inhibited it. Degradation of the [125I]A II present in the incubation medium was estimated by three different techniques. It increased linearly with time and reached 20% at 30 min. Specific binding of A II to human glomeruli at plasma concentrations observed in man under physiological conditions and during the iv administration of A II demonstrates that human renal glomeruli include target cells for A II and thus suggests a role for A II in regulation of the glomerular filtration rate in man.

Adult↗
PubMed1982

Stimulation of PGE2 synthesis by mercuric chloride in rat glomeruli and glomerular cells in vitro.

PGE2 production in the presence of mercuric chloride was measured by specific radioimmunoassay in isolated whole glomeruli and in cultured glomerular cells. Under basal conditions, mercuric chloride at 10 micrograms.ml-1 caused a twofold stimulation of PGE2 in isolated whole glomeruli, and at 1 to 10 micrograms.ml-1 it caused a more marked increase of PGE2 (eight times the control value) in mesangial or epithelial glomerular cells. An excess of arachidonic acid, however, blunted the stimulatory effects of mercury. Furthermore, the effect of mercuric chloride on PGE2 production was only observed with intact preparations but not with cell homogenates. Mercury inhibited cyclooxygenase activity in purified glomerular microsomes. It also inhibited phospholipase activity in purified glomerular cell membranes, whereas it stimulated phospholipase activity in intact cells. These results demonstrate that mercury modifies PGE2 synthesis via multiple mechanisms. Stimulation occurring at low doses of mercury can be attributed to the indirect activation of phospholipase. We suggest that mercuric chloride suppresses the inhibitory effect of lipomodulin on this enzyme.

Animals↗
PubMed1982

High plasma antidiuretic hormone in patients with cardiac failure: influence of age.

Plasma antidiuretic hormone (ADH) was greater in patients with cardiac failure than in healthy subjects. Plasma ADH increased significantly with age in both groups. Covariance analysis showed that the difference between patients and controls occurred whatever the age. Plasma sodium and plasma osmolality were lower in cardiac patients than in healthy subjects. This showed that increase in plasma ADH observed in patients was inappropriate since it coexisted with inhibitory levels of plasma osmolality. Plasma creatinine was greater in cardiac patients than in healthy subjects and for each group in elderly than in young people. But there was no significant correlation between plasma ADH and creatinine. This suggested that increase in plasma ADH observed in cardiac failure was due more to an augmented release than to a diminished catabolism. No clear influence of etiology, severity, length of the disease and treatment with diuretics could be demonstrated.

Adolescent↗
PubMed1981

Stimulation by oxygen radicals of prostaglandin production by rat renal glomeruli.

Polymorphonuclear leukocytes secreting oxygen radicals are found in the glomerular capillaries at an early stage of experimental acute glomerulonephritis. The aim of this work was to study the effects of these radicals on prostaglandin (PG) production by the glomeruli. Glomeruli were isolated from rat renal cortex and incubated in the presence of a biochemical system capable of generating oxygen radicals (addition to 100 microM xanthine of increasing concentrations of xanthine oxidase). Synthesis of PGE2, PGF2alpha, 6 keto PGF1alpha, and TXB2 estimated using specific radioimmunoassays was twofold greater in the presence of oxygen radicals. This effect was inhibited by catalase, slightly stimulated by superoxide dismutase, unaffected by hydroxyl radical scavengers, thus suggesting that hydrogen peroxide was the by-product responsible. This was confirmed by the stimulatory effect of hydrogen peroxide itself (1 to 100 microM) on PG synthesis. The effect of mepacrine, an inhibitor of phospholipase activity, on PG production was more marked in the presence of hydrogen peroxide and the stimulation of PG synthesis by hydrogen peroxide or oxygen radicals was progressively inhibited in the presence of arachidonic acid. Moreover, oxygen radicals stimulated the release of 14C-arachidonic acid previously incorporated in isolated glomeruli. This demonstrates that the increase in PG synthesis in response to oxygen radicals is due to activation of glomerular phospholipase by these radicals. This effect that is likely to occur at an early stage of experimental glomerulonephritis could play a role in the mechanism of the inflammatory process.

Animals↗
PubMed1981

Altered PGE2 and PGF2 alpha production by glomeruli and papilla of sodium-depleted and sodium-loaded rats.

Prostaglandin (PG) E2 and F2 alpha synthesis by isolated glomeruli and papillary homogenates prepared from control, salt-loaded, and salt-depleted rats was measured in vitro with and without added arachidonic acid using specific radioimmunoassays. Glomeruli from salt-depleted rats synthesized less PGE2 and more PGF2 alpha than glomeruli from control rats under both conditions. The effect of sodium restriction could be attributed to stimulation of glomerular 9-keto-PGE2 reductase activity unrelated to a change in the concentration of this enzyme. High salt diet had no effect on PG synthesis by glomeruli. Papillary homogenates prepared from salt-loaded rats synthesized more PGE2 than those from control rats both with and without added arachidonic acid. This finding suggests an effect of high salt diet at a stage further than phospholipid deacylation. Low salt diet had no effect on PG synthesis by papillary homogenates. The physiological control of PG synthesis in response to changes in the NaCl content of the diet is, therefore, different for the glomeruli and the papilla.

Animals↗
PubMed1981

Prostaglandin synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure.

In vitro PG synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure (ARF) was measured by radiometric high performance liquid chromatography after incubation with [14C]arachidonic acid and radioimmunoassay (RIA). The four PGs, 6-keto-PGF1 alpha, TXB2, PGF2 alpha, and PGE2 were each synthesized by glomeruli from both control and treated rats but the synthesis rates were greater after glycerol. This increase was not apparent 1 hour after injection but, at 24 hours, all PGs were produced in greater amounts by glomeruli of treated rats. Thus, we studied PGE2, PGE2 alpha, and TXB2 synthesis by glomeruli at various time intervals after induction of ARF using direct RIA, PGF 2 alpha and TXB2 synthesis were greater only at 24 hours and only in the presence of arachidonic acid, whereas PGE2 synthesis was greater at 24 hours, irrespective of arachidonic acid, but at 48 hours only with arachidonic acid. The stimulatory effect of arachidonic acid was always greater in glycerol-treated than in control rats for these three PGs in the later period, whereas a significant decrease for PGE2 was observed at 1 hour. The late increase in PG synthesis may be due to stimulation of the renin-angiotensin system since it was abolished in rats pretreated for 48 hours with captopril. A late increase in PG synthesis by the papilla of the treated rats also was observed. We concluded that any increase in the glomerular production of vasoconstrictor PGs could contribute to the maintenance of acute renal failure, whereas the early fall in the stimulatory effect of arachidonic acid on PGE2 synthesis could play a role in its initiation.

Acute Kidney Injury↗