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Biomedical subjects

R Ardaillou

Publications and source records attributed to R Ardaillou.

At least 145 records · Page 8Linked to original sources
PubMed1985

Stimulation of guanylate cyclase by atrial natriuretic factor in isolated human glomeruli.

A 23 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) stimulated guanylate cyclase activity in isolated human glomeruli in a concentration- and time-dependent manner. ANF activated particulate guanylate cyclase whereas it had no effect on soluble guanylate cyclase. These results demonstrate that the glomerulus is a target structure for ANF in humans. They also suggest that ANF-induced increase in glomerular filtration rate is due to a direct effect of this peptide on the glomerular cells mediated by activation of glomerular guanylate cyclase.

Atrial Natriuretic Factor↗
PubMed1985

Lipoxygenase products mediate the attachment of rat macrophages to glomeruli in vitro.

Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, we have studied the binding of [3H]-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective. Glomeruli interacted with macrophages in converting arachidonic acid (C20:4) to prostaglandins (PG) since productions of 6 keto-PGF1 alpha, TXB2, and PGD2 by glomeruli and macrophages incubated in combination were much greater than the sums of their respective productions by glomeruli and macrophages incubated separately. Macrophages were the source of the supplementary synthesis of PG which was abolished when these cells were pretreated with aspirin. Stimulation of macrophages by glomeruli was blunted by pretreatment of glomeruli with NDGA. Production of PG and of 12-HETE by macrophages was stimulated by a lipid extract of glomeruli containing the oxygenated metabolites of C20:4. Direct addition of 12-HPETE also stimulated macrophage functions. These data suggest that macrophage attachment to glomeruli and macrophage stimulation in the presence of glomeruli depend on glomerular lipoxygenase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Antidiuretic hormone response to volume depletion in diabetic patients with cardiac autonomic dysfunction.

Thirty-three insulin-dependent diabetic patients were separated into two groups from the results of three different tests for cardiac vagal neuropathy: heart rate response to deep breathing, Valsalva manoeuvre and heart rate response to postural change. Seventeen patients were considered as without ('intact' patients) and 16 as with ('denervated' patients) cardiac autonomic dysfunction. One patient with a transplanted heart was also studied. Plasma antidiuretic hormone (ADH), plasma aldosterone and plasma renin activity (PRA) were measured immediately before and 60 min after intravenous administration of frusemide and passage from lying to standing. The kinetics of hormonal responses were analysed more precisely (five blood collections) in six patients of each group who were studied again. Heart rate and blood pressure were recorded before each blood collection. Volume depletion estimated from the rise in plasma protein (+ 11.9 and + 12.2% in 'denervated' and 'intact' patients respectively) and heart rate response (+ 1.06 and + 14.7%) were similar in both groups. Mean blood pressure was unchanged in the 'intact' patients whereas it fell in the 'denervated' patients (-13.5%). PRA (+ 161.5 and + 231.2% in 'denervated' and 'intact' patients respectively) and plasma aldosterone (+ 318.2 and 279%) increased in both groups whereas plasma ADH was stimulated only in 'intact' patients (+ 55.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Vasoconstrictor-evoked prostaglandin synthesis in cultured human mesangial cells.

We examined the influence of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on prostaglandin (PG) synthesis and cell contractility in human glomerular mesangial cells in culture. Addition of sodium butyrate to the culture medium for 40 h significantly increased synthesis of both 6-keto-PGF1 alpha and PGE2 in the presence of exogenous arachidonic acid and of PGE2 under basal conditions. To optimize conditions in all further experiments, cells cultured with butyrate were studied. Under basal conditions, cultured mesangial cells produced predominantly 6-keto-PGF1 alpha and much less PGE2. Addition of either ANG II, AVP, or PAF all resulted in a rapid (within minutes) two- to threefold stimulation of 6-keto-PGF1 alpha and PGE2. Threshold stimulations were obtained at 10 pM for ANG II, 1 nM for AVP, and 10-100 pM for PAF. Preincubation of the cells with [Sar1,Ala8]ANG II, an antagonist of ANG II, inhibited ANG II-enhanced PG production, and preincubation with 1-desamino-8-D-arginine vasopressin, an antidiuretic analogue, blunted AVP-enhanced PG production. Under phase-contrast microscopy, PAF, ANG II, and, to a lesser degree, AVP caused decrease in cell surface area of mesangial cells cultured without butyrate at concentrations similar to those stimulating PG synthesis. Only PAF contracted cells cultured with butyrate, indicating attenuation of the vasoactive effects of ANG II and AVP when synthesis of PG was increased. However, a lower dose of PAF was only active when PG synthesis was inhibited, suggesting the same feedback mechanism for the three agonists.

Angiotensin II↗
PubMed1985

Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.

In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. [3H]LTC4 bound rapidly at 8 degrees C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of [3H]LTC4 and of the competition between a single concentration of [3H]LTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED50 values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.

Cell Division↗
PubMed1984

Solubilization of angiotensin II receptors in rat glomeruli.

125I-labelled angiotensin II (A II) specifically binds to solubilized receptors extracted from rat isolated glomeruli using CHAPS (3-[3-( cholamidopropyl ) dimethylammonio ]-1-propanesulfonate). The yield of solubilization of the binding sites was 3.3%. Equilibrium was reached after 15-20 min and specific binding represented 75% of total binding. Dissociation of the hormone-receptor complex after addition of an excess of A II was very slow in the presence of Ca2+ and Mg2+. [Sar1 Ala8] A II and [Sar1 Ile8] A II were more potent as competitive inhibitors of 125I-labelled A II than A II itself and its heptapeptide. These basic features of 125I-labelled A II binding to the extracted material were similar to those observed previously with untreated glomeruli.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1984

Glomeruli cooperate with macrophages in converting arachidonic acid to prostaglandins and hydroxyeicosatetraenoic acids.

The interaction of proliferating macrophages with the glomerulus may play an important role in certain forms of glomerulonephritis. This interaction could involve metabolites of arachidonic acid (C20:4) such as prostaglandins (PG) and lipoxygenase products. We therefore investigated the conversion of exogenous [3H] C20:4 into hydroxyeicosatetraenoic acids (HETE) and PG by isolated glomeruli and macrophages from rats, alone and in combination. As demonstrated by HPLC, glomeruli converted C20:4 predominantly to lipoxygenase products -mainly 12-HETE- and, to a lesser extent, to PG. Resident macrophages converted C20:4 to equivalent amounts of HETE and PG, mainly 12-HETE and 6 keto-PGF1 alpha. When macrophages and glomeruli were studied in combination, a striking interaction was detected in both pathways of C20:4 metabolism. Production of 6 keto-PGF1 alpha was stimulated and considerable amounts of TXB2, PGD2 and hydroxyheptadecatrienoic acid (HHT) were also produced. Total 12-HETE production was unchanged. When a lipid extract of glomeruli, containing oxygenated metabolites of C20:4, was added to macrophages, stimulation of 12-HETE occurred without any change in HHT or PG formation. When, on the contrary, a lipid extract from macrophages was added to glomeruli, 12-HETE production by the glomeruli was nearly completely abolished. Thus the unchanged total 12-HETE production by coincubated glomeruli and macrophages resulted from its increased production by macrophages and its decreased production by glomeruli. These data suggest that interaction between glomeruli and macrophages results in activation of C20:4 metabolism by macrophages followed by inhibition of C20:4 metabolism by glomeruli. Such a regulatory process could play a role in the inflammatory response to immunological injuries during macrophage-dependent human and experimental glomerulonephritis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

Renal excretion of antidiuretic hormone in healthy subjects and patients with renal failure.

Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease. In healthy subjects studied under conditions of mild water diuresis plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 +/- 0.36 pg/ml, 25.2 +/- 5.5 pg/min, 7.5 +/- 1.2 ml/min and 6.4 +/- 1.0% (means +/- SEM) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 +/- 0.19 pg/ml, 9.4 +/- 2.0 pg/min, 3.4 +/- 0.6 ml/min and 10.0 +/- 2.9% (means +/- SEM) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 +/- 0.47 pg/ml, 52.8 +/- 15.8 pg/min, 9.5 +/- 2.7 ml/min and 24.9 +/- 4.4% (means +/- SEM) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Antidiuretic hormone response to osmotic stimulus under fentanyl anaesthesia.

The effect of fentanyl anaesthesia on the plasma antidiuretic hormone (ADH) response to osmotic stimulus was studied in eight patients. Eight g (137 mmol) NaCl were rapidly injected intravenously the day before anaesthesia and blood samples were collected 5, 10, 20 and 30 min after the injection. This protocol was repeated in the same subjects, under anaesthesia with thiopental, nitrous oxide and fentanyl before surgical incision. Plasma ADH markedly increased after NaCl administration and was significantly correlated with plasma sodium (r = 0.67, P less than 0.005) when the patients were awake, whereas it did not change over 30 min and was not correlated with plasma sodium (r = 0.18, P greater than 0.05) under fentanyl anaesthesia. This inhibitory effect of anaesthesia occurred in spite of a significant fall in the mean arterial pressure during the study. In order to eliminate the role of overnight fasting, premedication and fluid load, the same protocol was performed in six control patients who were fasted overnight, premedicated and fluid loaded. These results demonstrate that fentanyl anaesthesia abolishes the plasma ADH response to both osmotic and low arterial pressure stimuli.

Adult↗
PubMed1984

Role of antidiuretic hormone in impaired water excretion of patients with congestive heart failure.

Plasma antidiuretic hormone (ADH), PRA, plasma osmolality, and the parameters of renal water excretion were measured after overnight dehydration and for 5 h after an oral load in 14 patients with congestive heart failure (CHF) treated with diuretics (group 1), 8 hypertensive patients without CHF also treated with diuretics (group 2), and 11 patients with coronary artery disease but without CHF who were not treated with diuretics (group 3). Under basal conditions, mean plasma osmolality was lower in group 1 than in group 3, but was not different in groups 1 and 2. Mean plasma ADH was higher in group 1 than in group 2 or 3. In response to the water load, plasma osmolality and plasma ADH levels decreased in the 3 groups. ADH levels remained significantly greater in group 1 than in groups 2 and 3 from 2-4 h after the water load despite more marked hypoosmolality in group 1 compared with that in either of the 2 control groups. Plasma ADH was significantly correlated with plasma osmolality only in the 2 control groups. Mean PRA was greater in patients with CHF and patients without CHF treated with diuretics than in untreated patients. Cumulative water excretion was lower in patients with CHF than in patients in the 2 control groups from 2-5 h after the water load. At 5 h, the mean percentage excretion of the ingested loads was 56.8%, 90.7%, and 91.2% in the patients of groups 1, 2, and 3 respectively. Free water clearance was lower and minimal urinary osmolality was greater in the patients with CHF than in those in the 2 control groups. Two patients with CHF, who excreted more than 75% of the water load, also had low plasma basal ADH levels. These data show that patients with CHF have an inappropriate response of plasma ADH to a marked fall in plasma osmolality. This disorder is not due to the diuretic therapy, since hypertensive patients treated with diuretics behaved similarly to untreated patients without CHF. The reasons for this inappropriate response of plasma ADH during a water load in patients with CHF are probably multifactorial.

Adult↗
PubMed1984

Effects of an acute calcium load on plasma ACTH, cortisol, aldosterone and renin activity in man.

Plasma adrenocorticotrophin (ACTH), cortisol and aldosterone increased during and after iv administration of calcium gluconate in 4 normal subjects, one patient with hypoparathyroidism and one patient with hypothyroidism. On the other hand, there was a decrease in plasma renin activity but only in the normal subjects. Plasma ACTH and cortisol responses to calcium were abolished whereas plasma aldosterone response persisted in 2 normal subjects pre-treated with dexamethasone. The results observed after calcium administration were compared to those observed after infusion of the solvent only in 6 normal subjects and 4 thyroidectomized patients who were studied twice at 3 day intervals. Plasma ACTH, cortisol and aldosterone were higher when calcium was administered. Plasma renin activity was not statistically different whether or not calcium had been injected in the subjects studied twice. These results demonstrate a direct effect of calcium on ACTH and aldosterone secretion which is not mediated by calcitonin and parathyroid hormone. The stimulatory effect of calcium on cortisol secretion depends on the increase in plasma ACTH.

Adrenocorticotropic Hormone↗
PubMed1983

Reactive oxygen production by cultured rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity.

To investigate the phagocytic capability of glomerular mesangial cells and the biochemical events associated with phagocytosis, rat cultured mesangial cells were incubated in the presence of opsonized zymosan (STZ) and production of reactive-oxygen species and lipoxygenase products were determined. Mesangial cells were identified on the basis of morphologic (presence of microfilaments and pattern of staining by an anti-myosin antiserum) and physiologic (contractile activity in response to angiotensin II) characteristics. No contamination by esterase-positive cells was observed. Electron microscopy revealed that the phagocytic process started after 5 min of incubation, and affected approximately 50% of the cells. Superoxide anion (.O2-) and hydrogen peroxide (H2O2) generation by mesangial cells exposed to STZ increased with time and STZ concentration. Cells incubated with zymosan particles treated with heated serum produced undetectable amounts of .O2- and 6 times less H2O2 than cells exposed to STZ. Pretreatment by cytochalasin B produced a marked decrease in STZ-stimulated production of reactive oxygen species. [3H]Arachidonic acid was incorporated into mesangial cell phospholipids and its release and conversion into monohydroxyeicosatetraenoic acids (HETE) was measured by radiometric high performance liquid chromatography (HPLC). Incubation with STZ markedly stimulated the release of arachidonic acid from its phospholipid stores and its transformation into 11-, 12-, and 15-HETE. Lipoxygenase inhibitors inhibited STZ-stimulated H2O2 production, whereas they did not modify the phagocytic process as shown by the absence of any effect on the uptake of 125I-STZ by the mesangial cells. This study demonstrates that a high percentage of rat cultured mesangial cells phagocytose opsonized particles. The phagocytic process results in an oxidative burst that appears to be dependent on stimulation of the lipoxygenase pathway.

Animals↗
PubMed1983

Metabolism of arachidonic acid via the lipoxygenase pathway in human and murine glomeruli.

Glomeruli isolated from murine and human renal cortex metabolize arachidonic acid to prostaglandins via the cyclooxygenase pathway but whether such glomeruli can also metabolize arachidonic acid via the lipoxygenase pathway is controversial. [1-14C]Arachidonic acid was incubated with glomeruli or glomerular fractions isolated from rat and human renal cortex. The products were extracted, purified by high performance liquid chromatography, and identified by comparison of their retention times with those of authentic hydroxyeicosatetraenoic acid (HETE) standards and by gas chromatography-mass spectrometry. At low substrate concentrations, human glomeruli synthesized in equivalent amounts 12- and 15-HETE, whereas rat glomeruli synthesized only 12-HETE and in larger quantities than in man. At higher substrate concentrations, both species synthesized 12- and 15-HETE and the rate of synthesis for both products was higher in human glomeruli. No other HETE was detected in either species. The lipoxygenase products were stored within the glomeruli and recovered almost equally in the 10,000 x g pellet and in the 100,000 X g supernatant of the homogenized glomeruli. The properties of the lipoxygenase system were the following: the enzyme was distributed equally in the membranes and the cytosol; 12-HETE accumulation was linear with time over 15 min; and 12-HETE production correlated linearly with the amount of glomerular protein. 12-Lipoxygenase activity was maximum at pH 7.5 (rat) or 9.0 (human) and at 40-42 degrees C (both species). Km values calculated at low concentrations of substrate (10-200 microM) were for 15-HETE, 125 and 667 microM with murine and human glomeruli, respectively, and for 12-HETE, 44 microM with the glomeruli of both species. This study demonstrates lipoxygenase activity in murine and, for the first time, in human glomeruli. The products of such enzymatic activity, 12- and 15-HETE, may mediate the glomerular inflammatory response in various experimental or spontaneous glomerular diseases.

Animals↗
PubMed1983

Prostaglandin synthesis by human glomerular cells in culture.

PG synthesis by cultured human glomerular mesangial and epithelial cells incubated with [1- 14C] arachidonic acid was determined by radioimmunoassay (RIA) after high performance liquid chromatography purification. Both dissociated cells and cell monolayers were studied under basal conditions. PG synthesis by epithelial cells was undetectable. Mesangial cells produced low amounts of PGE2, PGF2 alpha and 6 keto-PGF1 alpha and no TXB2. We also examined the effects of several agents on PG synthesis in these two types of cells scraped away from their flasks using direct RIA. Arachidonic acid produced a slight stimulation only with mesangial cells whereas angiotensin II, cyclic AMP and calcium ionophore were inactive with both cell lines. Homogenization of the cells did not enhance the stimulatory effect of arachidonic acid. Alkalinization of the incubation medium produced an increase of PG production by mesangial cells. These results suggest that two types of human glomerular cells, particularly epithelial cells, possess low cyclooxygenase activity. The low capacity of human mesangial and epithelial cells to produce PG may have consequences for the endocrine control of the glomerular microcirculation in man.

Arachidonic Acid↗