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Biomedical subjects

R Ardaillou

Publications and source records attributed to R Ardaillou.

At least 127 records · Page 7Linked to original sources
PubMed1987

Human glomeruli release fatty acids which stimulate thromboxane synthesis in platelets.

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1987

Changes in plasma renin, insulin, aldosterone and arginine vasopressin during plasmapheresis.

1. Nineteen patients with a spectrum of immunologically related disorders were studied before and immediately after plasmapheresis for changes in plasma aldosterone, insulin and arginine vasopressin (AVP). Renin was also measured in 11 of these patients by direct radioimmunoassay. 125% of the initial plasma volume was replaced, which corresponded to a predicted removal of 72% for any plasma constituent. 2. The initial, final (experimental) and final (predicted) concentrations (means +/- SEM) were 337 +/- 50, 185 +/- 23 and 100 +/- 16 pg/ml respectively for renin, 465 +/- 86, 146 +/- 38 and 124 +/- 22 pmol/l respectively for aldosterone, 218 +/- 35, 69 +/- 11 and 63 +/- 11 pmol/l respectively for insulin, 7.2 +/- 1.9, 6.1 +/- 0.5 and 1.8 +/- 0.2 pmol/l respectively for AVP. The predicted final concentration was calculated from the initial concentration and the fraction of plasma volume exchanged. The experimental final concentration was lower than the initial concentration for renin, aldosterone and insulin (P less than 0.001) but not for AVP. The predicted final concentration was lower than the experimental final concentration for AVP and renin (P less than 0.001) but not for aldosterone and insulin. Plasma volume, osmolality, glucose, sodium and potassium concentrations did not change significantly. 3. The concentrations of renin, aldosterone, insulin and AVP in the removed plasma were 84 +/- 17 pg/ml, 179 +/- 36, 98 +/- 15 and 4.8 +/- 0.7 pmol/l respectively. The amount subtracted expressed as percentage of the total amount present in plasma was markedly greater for AVP than for the three other plasma constituents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Identification and regulation of renin in human cultured mesangial cells.

Renin activity was measured in the incubation medium, and the cellular extract of human mesangial cells, which had been cultured in the presence of renin-free human plasma (three kidneys; 4-7 passages). Active renin and total renin obtained after trypsin treatment was estimated by radioimmunoassay of angiotensin I using renin-free human plasma as a substrate. Mesangial cell renin had characteristics similar to those of standard human renin; optimum enzymatic activity at pH 5.8, marked inhibition in the presence of two (monoclonal and polyclonal) human renin-specific antibodies and of SR 42128, a new potent statine-containing renin inhibitory peptide. The synthetic capability of the mesangial cells varied markedly with the original kidney (1-49 and 0.3-0.9 ng X h-1 X mg-1 for total renin in the medium and the cellular extract respectively). Renin was secreted mainly as inactive renin. Prostaglandin E2 (PGE2) and carba-prostaglandin I2 (PGI2) (a stable analogue) produced a dose-dependent (0.1-1.10 microM) increase in renin activity in both the cellular extract and the culture medium. Isoproterenol (200 microM) increased renin activity only in the medium. The effects of these agonists were more marked on inactive than on active renin. These results demonstrate that cultured human mesangial cells synthesize and release renin in a stable manner over a long period of culture, thus providing a useful tool for the in vitro study of renin secretion and its control.

Cells, Cultured↗
PubMed1987

Massive plasma arginine vasopressin (AVP) removal during hemofiltration stimulates AVP secretion in humans.

Arginine vasopressin (AVP) was measured in the plasma and its ultrafiltrate in 11 patients with end-stage renal failure treated by hemofiltration. Nineteen liters of ultrafiltrate were produced in 170 min and continuously replaced by an isoosmotic substitution fluid to maintain constant body weight. Plasma and ultrafiltrate AVP concentrations were not significantly different and did not change with time. The AVP clearance rate due to hemofiltration was 114 +/- 2.6 (+/- SE) ml/min, which represented more than two thirds of the predicted MCR in these patients. Corrected plasma osmolality, body weight, mean blood pressure, hematocrit, and PRA did not change during the hemofiltration session. These results indicate that there is a compensatory increase in AVP production which maintains plasma AVP unchanged in response to the increased MCR resulting from hemofiltration. The responsible stimulus could be a direct effect of the decrease in plasma AVP on the AVP-secreting neurones. Alternatively, ultrafiltration itself, via the hemodynamic changes it produces or the loss of an unrecognized inhibitory substance, may be the stimulus to AVP secretion.

Adult↗
PubMed1987

Role of cardiac parasympathetic dysfunction in atrial natriuretic peptide response to volume changes in patients with chronic renal failure.

Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay in 10 patients with end-stage renal failure during two successive 150-min periods of ultrafiltration and perfusion of an identical fluid volume (1,800-2,400 ml). The patients were divided into two groups of 'denervated' and 'intact' patients based on three different tests for cardiac parasympathetic dysfunction. Plasma ANP was higher in the denervated group than in the intact group throughout all the study, but decreased with the volume ultrafiltered and increased with the volume perfused in both groups. The sensitivity of ANP response to perfusion was greater in denervated than in intact patients. These results demonstrate the close relationship between plasma ANP and stepwise decremental or incremental changes in extracellular fluid volume. They also suggest that cardiac parasympathetic innervation plays a role in modulation of ANP secretion in humans.

Adult↗
PubMed1987

Renal response to volume expansion in heart-transplant and kidney-transplant recipients.

The renal excretion of an intravenous sodium load by ten heart-transplant recipients with (five patients) or without (five patients) moderate renal failure was compared with the results obtained in two matched control groups of ten kidney-transplant recipients with similar renal function. All patients were treated with prednisone and cyclosporine except, for the latter treatment, the kidney-transplant recipients without renal failure. A supplementary control group of five healthy subjects who did not receive any treatment was also included in the study. Fractional sodium and osmolal clearances were greater in heart-transplant than in kidney-transplant recipients for both the patients with and the patients without renal failure. These two parameters were also greater in heart-transplant recipients without renal failure than in healthy subjects. Free water clearance was smaller in the heart-transplant recipients than in the corresponding control patients. Fractional potassium clearance was not different from group to group. These results demonstrate that heart-transplant recipients excrete a greater fraction of the filtered sodium load than their controls. This increased fractional excretion of sodium cannot be attributed to the cyclosporine treatment or the moderate chronic renal failure which both have been taken into account in the comparisons. The unchanged blood pressure during the saline load and the high or normal plasma renin activity levels in the heart-transplant recipients make it also unlikely that the exaggerated natriuresis was the consequence of the higher blood pressure observed in these patients. The chronic cardiac denervation which is the consequence of surgery in these patients could play a role in the mechanism of the saline diuresis.

Adult↗
PubMed1986

Leukotrienes and other lipoxygenase products of arachidonic acid synthesized in the kidney.

Lipoxygenase products are synthesized in the kidney. Rabbit medulla and murine and human glomeruli produce 12- and 15-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE). Minor amounts of leukotrienes are formed under normal conditions, but it is likely that the resident renal cells are capable of synthesizing these metabolites. Rat glomeruli and papillae possess the enzymes necessary to process leukotriene C4 into leukotrienes D4 and E4. However, the enzyme activity of the papillae is masked due to the presence of an inhibitor detected in the 10,000 g supernate of the papillary homogenate. 12-HETE synthesis is markedly increased in glomeruli from rats with nephrotoxic serum nephritis and leukotriene B4 synthesis in glomeruli from rats with cationic bovine gamma-globulin-induced glomerulonephritis. In vivo consequences of the association between the resident glomerular cells and the bone marrow-derived cells have been studied in vitro in co-incubation experiments. Glomeruli release factors that stimulate the cyclo-oxygenase and lipoxygenase pathways in macrophages. Co-incubation of glomeruli, platelets, and polymorphonuclear leukocytes results in the formation of 12,20-diHETE and an excess of 12-HETE. Lipoxygenase products, regardless of their origin, modify the renal functions. Leukotriene C4 binds specifically to rat glomeruli and human cultured glomerular epithelial cells. Leukotrienes C4 or D4 administered in vivo cause renal vasoconstriction and a decline in the glomerular filtration rate. In vitro, these two sulfidopeptide leukotrienes promote epithelial cell proliferation and produce mesangial cell contraction. The lipoxygenase pathway is also implicated in the attachment of macrophages to glomeruli and in the oxidative burst of glomerular mesangial cells during phagocytosis. The future use of specific inhibitors of the synthesis or antagonists of the lipoxygenase products, particularly the leukotrienes, should provide a tool for evaluating the role of these metabolites in renal diseases.

Animals↗
PubMed1986

Stimulation of cyclic GMP synthesis in human cultured glomerular cells by atrial natriuretic peptide.

Recently a stimulatory effect of atrial natriuretic peptide (ANP) on the particulate guanylate cyclase system has been reported in the glomeruli from different species. Using cultures of homogeneous human glomerular cell lines, we found that rat and human ANP stimulated markedly cGMP formation in epithelial cells with a threshold dose of 1 nM. A 20-fold increase was obtained at 5 microM. Stimulation was also present but less substantial (2-fold at 5 microM) in mesangial cells. cGMP was formed rapidly and released in the medium. ANP and sodium nitroprusside, an activator of soluble guanylate cyclase, had additive effects on cGMP formation. ANP did not inhibit cAMP formation in both cell lines. These results demonstrate that, at least in the human species, epithelial cells represent the main target of ANP in the glomerulus. Synthesis of cGMP in the glomerular epithelial cells in response to ANP also suggests that the excess of urinary cGMP produced by the kidney which is observed after ANP administration is of glomerular rather than of tubular origin.

Atrial Natriuretic Factor↗
PubMed1986

Bioconversion of leukotriene C4 by rat glomeruli and papilla.

Since leukotriene C4 (LTC4) may be locally synthesized by bone marrow-derived cells infiltrating the kidney in inflammatory renal diseases we examined the in vitro metabolism of exogenously added [3H] LTC4 by rat glomeruli and papilla using radiometric HPLC. Homogenized as well as intact glomeruli converted [3H] LTC4 mainly into [3H] LTE4 (83%) and, at a smaller extent, into [3H] LTD4 (4%). Intact [3H] LTC4 represented 13% of the sum of radioactive leukotrienes. Addition of L-cysteine resulted in accumulation of LTD4. In contrast, there was nearly no conversion of [3H] LTC4 (87% intact) in the presence of homogenized papilla. The metabolism of [3H] LTC4 by the glomeruli was time- and temperature-dependent. The 10,000 g supernatant and pellet of homogenized glomeruli both retained the ability to metabolize [3H] LTC4. The papillary 10,000 g supernatant was inactive, as found for the total homogenate, whereas the papillary 10,000 g pellet separated from its supernatant could transform [3H] LTC4 into its metabolites, LTD4 and LTE4. Addition of increasing amounts of papillary 10,000 g supernatant to homogenized glomeruli progressively protected [3H] LTC4 from its bioconversion. These results demonstrate that both glomeruli and papilla possess the gamma-glutamyl transpeptidase and dipeptidase necessary to process LTC4. However, the enzyme activity of the papilla is unmasked only when the inhibitor present in the 10,000 g supernatant is separated from the enzyme present in the pellet.

Animals↗
PubMed1986

Prostaglandins and other arachidonic acid metabolites in the kidney.

This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this segment. These effects need not necessarily be reflected in the overall renal function. Also in some cases, the determinant may not be prostaglandins, that is, cyclooxygenase derivatives of AA, but perhaps lipoxygenase or epoxygenase products that influence the functional parameters of the specific segment. Despite the multitude of renal functions that may be influenced by PG, we would like to propose a teleological hypothesis for an overall role of PG in the kidney, that is, that of cytoprotective agents. Renal vasodilatatory prostaglandins will maintain renal blood flow when the latter is challenged, thus, preventing hypoxic injury to the tissue. Endogenous prostaglandins may also protect tubular cells from extreme environmental changes as may occur on both the luminal and contraluminal sides. For example, tubular cells may be exposed to luminal fluid that may vary from hypotonic to hypertonic, from alkaline to acid, and so forth. Similarly, the interstitial fluid osmolality and solute composition is subject to considerable variations which may be opposite to those existing on the urinary side. The role of PG might be to maintain the internal milieu of the cells exposed to such extreme changes in environment. This could be accomplished by changing the permeability characteristics of the membranes and the function of pumps. Thus, specific PGs could dampen the hormonal response to protect the specific nephron segment, which might otherwise suffer injury. This hypothesis might also help to explain why the effect of PG administration or inhibition of PG synthesis may vary considerably depending on the overall physiological state of the subject: Maintenance of a local internal milieu may require different responses from those required for total body homeostasis.

Animals↗
PubMed1986

Vasopressin, aldosterone and renin responses to volume depletion in heart-transplant recipients.

Plasma arginine vasopressin (AVP), renin activity (PRA) and aldosterone (ALD) were measured immediately before and 60 min after intravenous administration of frusemide and passage from lying to standing in 10 untreated healthy subjects (group 1), eight asthmatic patients treated with prednisone (group 2) and 13 heart-transplant recipients treated with prednisone and cyclosporin (group 3). Three different tests for cardiac vagal innervation were performed in the study population. They confirmed that the patients of group 3 were denervated whereas those of groups 1 and 2 had an intact cardiac innervation. Plasma volume depletion after frusemide administration estimated from the rise in plasma proteins was 10-12%. Mean blood pressure was higher in the transplant recipients but did not change in the three groups. Heart rate was also greater in the transplant recipients as a result of vagal denervation. PRA and ALD increased in all the subjects: 2.8, 3.3 and 2.2 times basal value for PRA, 2.7, 4.6 and 2.1 times basal value for ALD in groups 1, 2 and 3 respectively. In contrast, plasma AVP increased only in the two control groups (x1.45 and x1.65 in groups 1 and 2 respectively) whereas it was unchanged in the group of heart-transplant recipients (x1.05). In order to better understand the etiology of the high basal AVP plasma levels observed in group 3, AVP response to a standard water load was studied in eight supplementary heart-transplant recipients: 81.5% of the water load was excreted over 3 h and plasma AVP fell significantly (x0.76).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Dexamethasone and hydrogen peroxide production by mesangial cells during phagocytosis.

We have previously demonstrated that a high percentage of rat cultured mesangial cells phagocytized serum-treated zymosan (STZ) (L. Baud, J. Hagege, J. Sraer, E. Rondeau, J. Perez, and R. Ardaillou, J. Exp. Med. 158: 1836-1852, 1983). Phagocytosis resulted in stimulation of arachidonic acid metabolism with generation of H2O2. Exposure of mesangial cells to dexamethasone for 48 h produced a dose-dependent decrease in phagocytosis-induced production of H2O2 with a 50% inhibitory concentration of 32 nM. The decrease in H2O2 release was associated with the inhibition of prostaglandin (PG) E2 production. The effect of dexamethasone could be considered as due to receptor-mediated modulation of protein synthesis since dexamethasone was not active immediately but only after a lag period of 3 h; RU 38486, a potent competitor for dexamethasone receptors, counteracted the reduction in H2O2 generation; and actinomycin and cycloheximide both blunted the inhibitory effect of dexamethasone. Pretreatment of mesangial cells with dexamethasone also produced a dose-dependent decrease in the phagocytic capability of the cells (63% inhibition for 1 microM dexamethasone). However, the inhibitory effect of dexamethasone on H2O2 production expressed as percentage of control was similar whether or not phagocytosis had been blocked by cytochalasin B. This result and also the fact that dexamethasone inhibited H2O2 production in cells triggered with soluble stimuli (A 23187 ionophore, PAF) suggested that the effect of dexamethasone on H2O2 generation was independent of that on phagocytosis. Addition of exogenous arachidonic acid reduced the effect of dexamethasone only when its conversion into PGE2 was inhibited by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Reactive oxygen species: production and role in the kidney.

Reactive oxygen species (ROS) are formed by incomplete reduction of molecular oxygen. They include superoxide anion (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (OH.), and singlet oxygen (1O2). ROS may induce different types of cell injury, particularly lipid peroxidation and membrane damage. ROS have been shown to play an essential role in the mechanisms of experimental models of several renal diseases: ischemic acute renal failure, renal graft rejection, acute glomerulonephritis, and toxic renal diseases. They are produced by the renal cells and also by the inflammatory bone marrow-derived cells invading the renal tissue. ROS, regardless of their origin, may degrade the glomerular basement membrane and alter the glomerular and tubular cell functions. Particularly, they produce an increase in cyclic AMP synthesis and prostaglandin production in the glomeruli. Recent studies have shown that the glomerular mesangial cells themselves generated ROS on stimulation by phagocytosis of foreign particles or exposure to the complement membrane attack complex or platelet-activating factor. Production of ROS is in narrow relationship with the metabolism of arachidonic acid. Conversion of this fatty acid via the lipoxygenase pathway is associated with an increase of ROS, whereas its transformation into prostaglandins via the cyclooxygenase pathway results in the opposite effect. Production of ROS in activated mesangial cells can be inhibited by glucocorticoids via a receptor-mediated mechanism. The fact that some of these characteristics are different in leukocytes suggests the possibility in the future of the more specific pharmacological control of the inflammatory process in the glomerular mesangium.

Acute Disease↗
PubMed1986

Renal hemodynamic effects of tertatolol in essential hypertension.

Tertatolol, a new beta-blocker, and propranolol, considered a reference beta-blocker, were given orally (5 and 160 mg slow release, respectively) for 15 days to two groups of patients with essential hypertension in order to compare their effects on renal hemodynamics. Systolic and diastolic blood pressure, heart rate, and erect plasma renin activity fell significantly in both groups while prostaglandin E2 urinary excretion was unchanged. Tertatolol administration produced increases in glomerular filtration rate, as shown by inulin clearance (+8.9%; p = 0.038) and renal plasma flow, as shown by paraaminohippurate clearance (+13.0%; p = 0.007). In contrast, propranolol administration resulted in a slight decrease in glomerular filtration rate (-2.8%; not significant) and a fall in renal plasma flow (-13.4%; p less than 0.001). Comparison between both treatments showed that glomerular filtration rate and renal plasma flow were higher in the patients treated with tertatolol than in those treated with propranolol whereas filtration fraction was lower, which suggests that tertatolol causes a vasodilation of the glomerular afferent arteriole. These results demonstrate that in contrast to propranolol (160 mg), and despite both drugs exhibiting a comparable antihypertensive activity, tertatolol (5 mg) does not alter but even improves renal perfusion in hypertensive patients.

Adrenergic beta-Antagonists↗
PubMed1986

Arginine vasopressin in human follicular fluid.

Arginine vasopressin (AVP) was determined in plasma and follicular fluid in 28 women in an in vitro fertilization program. In 23 women, follicular fluid was collected by laparoscopy during general anesthesia, and in 5 women, it was collected transvaginally with no such anesthesia. Plasma AVP increased markedly from its basal (preanesthesia) value in the first group, whereas it did not change in the second group. AVP concentrations were approximately 10-fold lower in the follicular fluid than in the plasma collected simultaneously in the anesthetized women. AVP levels were not significantly different in plasma and follicular fluid in the women of the second group. AVP concentrations were similar in ovarian venous and brachial venous plasma in 4 women during surgery. These results indicate that AVP concentrations in follicular fluid are equal to or lower than those in plasma and that AVP concentrations are not higher in efferent blood from the ovary than in peripheral blood.

Adult↗