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R Ardaillou

Publications and source records attributed to R Ardaillou.

At least 55 records · Page 3Linked to original sources
PubMed1996

Characterization of a B2-bradykinin receptor in human glomerular podocytes.

We characterized bradykinin (BK) receptors in a human line of glomerular visceral epithelial cells (hGVEC) transfected by the SV40 virus. [3H]BK bound specifically in a manner consistent with a single high-affinity site. Scatchard analysis yielded dissociation constant and maximum binding values of 0.28 +/- 0.04 nM and 76.6 +/- 4.9 fmol/mg, respectively. Competition binding studies with selective BK type 2 (Hoe-140) receptor antagonist and type 1 ([des-Arg9]BK) receptor agonist showed that hGVEC only expressed type 2 receptors, and this was confirmed by reverse transcriptase-polymerase chain reaction and ribonuclease protection assay. BK stimulated intracellular calcium ion concentration ([Ca2+]i) release in a dose-dependent manner with a threshold at 1 nM. Hoe-140, in contrast with [des-Arg9]BK, abolished this effect. [Ca2+]i stimulation was also inhibited by thapsigargin, an inhibitor of Ca(2+)-adenosinetriphosphatase. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid attenuated but did not suppress the [Ca2+]i peak. These results associated with the stimulatory effect of BK on inositol phosphate production indicated that [Ca2+]i stimulation was produced both by [Ca2+] mobilization from its intracellular stores and by [Ca2+] entry into the cells. In conclusion, hGVEC express specific type 2 BK receptors that enable specific BK-induced responses.

Binding Sites↗
PubMed1996

Regulation of angiotensin II receptor subtypes by dexamethasone in rat mesangial cells.

The objective of this study was to examine the role of dexamethasone on the expression of angiotensin II (Ang II) receptors in cultured rat mesangial cells. Dexamethasone caused concentration- and time-dependent decreases in 125I-[Sar1,Ala8]Ang II binding that were prevented by glucocorticoid receptor inhibition with mifepristone. A lag time of 24 hours and a dexamethasone concentration of at least 10 nmol/L were necessary for this effect to occur. Dexamethasone-induced reduction of 125I-[Sar1,Ala8]Ang II binding resulted from decreased Ang II type 1 (AT1) receptor density. No change in the apparent dissociation constant was observed. Dexamethasone also markedly inhibited Ang II-dependent inositol phosphate accumulation. Both reverse transcription-polymerase chain reaction and Northern blot analysis using specific short probes from the 3' noncoding region of the cDNA demonstrated the presence of AT1A and AT1B receptor mRNAs in rat mesangial cells, with a slight predominance of AT1B. Therefore, we studied the effect of dexamethasone on the expression of these two subtypes in rat mesangial cells. Dexamethasone produced a time-dependent decrease of AT1B receptor mRNA that was apparent after 6 hours of incubation, whereas AT1A receptor mRNA did not change. Mifepristone also suppressed the dexamethasone-induced decrease in AT1B receptor mRNA. In conclusion, glucocorticoids diminish Ang II receptor density at the mesangial cell surface through a mechanism that implies successive interaction with the glucocorticoid receptor and specific reduction in AT1B receptor mRNA expression. This differential regulation of both AT1 receptor subtypes might allow glucocorticoids to exert adjusted effects in their various target tissues.

Angiotensin II↗
PubMed1996

[Angiotensin IV, a new component of the renin-angiotensin system, which acts on kidney cells].

Angiotensin IV (Ang IV), the hexapeptide obtained from angiotensin II (Ang II) by deletion of the first two N terminal amino acids, possesses specific receptors in various tissues. Our aim was to search for such receptors in two types of renal cells, rat mesangial cells and principal cells of the human collecting duct. [125I]-Ang IV specifically bound to mesangial cell surface and to membranes prepared from the principal cells. In both cases, affinity was approximately 5 nmol/L and receptor density was close to 1000 fmol/mg protein. The order of potency of different competitors was as follows: Ang IV > Ang III > Ang II > Ang II (4-8) > Ang II (1-7). Binding sites were distinct from those of Ang II since type 1 or type 2 Ang II receptor nonpeptide antagonists produced no displacement. Reciprocally, Ang IV did not displace Ang II from its binding sites. Ang IV inhibited the vasoconstrictor effect of Ang II on rat mesangial cells and increases cyclic AMP production in principal cells, but only when it had been previously stimulated. Taken together, these results demonstrate that the glomerulus and the collecting duct represent target sites for Ang IV and suggest that Ang IV could influence the renal functions.

Amino Acid Sequence↗
PubMed1995

Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats.

In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

The effect of increased salt intake on blood pressure of chimpanzees.

A colony of 26 chimpanzees given a fruit and vegetable diet of very low Na and high K intake were maintained in long-standing, socially stable small groups for three years. Half of them had salt added progressively to their diet during 20 months. This addition of salt within the human dietetic range caused a highly significant rise in systolic, mean and diastolic blood pressure. The change reversed completely by six months after cessation of salt. The effect of salt differed between chimpanzees, some having a large blood pressure rise and others small or no rise. These results in the species phylogenetically closest to humans bear directly on causation of human hypertension, particularly in relation to migration of preliterate people, with low Na diet, to a Western urban lifestyle with increased salt intake. The hedonic liking for salt and avid ingestion was apt during human prehistory involving hunter-gatherer-scavenger existence in the interior of continents with a scarcity of salt, but is maladaptive in urban technological life with salt cheap and freely available.

Animals↗
PubMed1995

Tumor necrosis factor in renal injury.

Inflammatory diseases of the renal glomerulus and tubulointerstitium are characterized by destructive and restorative processes. These alterations are mediated by soluble molecules, including cytokines that instruct target cells to alter their proliferation, differentiation phenotype, secretion and migration. One of these cytokines is tumor necrosis factor-alpha (TNF alpha). Its expression within the glomerulus has been observed in both resident cells and infiltrating monocytes/macrophages in response to cell stimulation with chemicals, immune complexes, bacterial lipopolysaccharides, and advanced glycosylation end products. Its release can be amplified by deposits of terminal complement proteins (C5b-9) or formation of platelet-activating factor and reactive oxygen species, and, on the contrary, blunted by that of prostaglandins or anti-inflammatory interleukin (IL)-6 and IL-10. The roles of TNF alpha in the pathogenesis of glomerular diseases include reduction of blood flow and filtration rate, alteration of the barrier function of capillary wall, formation of capillary thrombi and infiltration of the structure by blood-borne cells. Expression of TNF alpha has been observed in tubulointerstitium as well, mainly in proximal tubular epithelial cells. In vitro, this expression can be amplified by IL-1 and, inversely, suppressed by immunosuppressive drugs. Roles of TNF alpha in tubulointerstitium remain largely undefined, but may include infiltration of the interstitium by inflammatory cells and alteration in tubular transport of fluid and electrolytes. Extensive study will be necessary to further elucidate intracellular signals induced by TNF alpha binding to target cells within the kidney and thus to establish possibilities of therapeutic intervention.

Animals↗
PubMed1995

[Production and proinflammatory activity of tumor necrosis factor alpha in the glomerulus].

The production and the effects of tumor necrosis factor alpha (TNF alpha) have been studied in isolated glomeruli and cultured glomerular cells from animal or human origin. Glomeruli from rats injected with E. coli lipopolysaccharide (LPS) and glomeruli exposed to LPS in vitro release TNF alpha into the medium. The glomerular cells responsible for TNF alpha synthesis are mesangial cells. Production of TNF alpha is controlled by other locally produced mediators. Prostaglandin E2 and interleukin-10 are inhibitory. Hydroxyl radicals stimulate the transformation of the transmembrane form of TNF alpha into its soluble form which is secreted into the medium. TNF alpha acts on its producing cells and on the neighbouring cells. It induces contraction of mesangial cells, increases the synthesis of a variety of local mediators including prostaglandins, platelet-activating factor and chemotactic agents, particularly interleukin-8. Synthesis of this cytokine implies activation of tyrosine kinase and of transcription factors, essentially NFkB. Taken together, these results suggest that TNF alpha plays a marked role in the development of glomerular injury and incite us to search for treatments inhibiting its synthesis and its effects.

Animals↗
PubMed1994

Characterization of C-type natriuretic peptide receptors in human mesangial cells.

Our aim was to examine whether the human glomerulus was a target for C-type natriuretic peptide (CNP) and how A, B and C receptors of natriuretic peptides (ANPR-A, ANPR-B, ANPR-C) were distributed in glomerular mesangial and epithelial cells. CNP stimulated cyclic GMP production in cultured human mesangial and epithelial cells with similar threshold concentrations (1 nM) and maximum effects (basal value x 30 at 1 microM). In contrast, atrial natriuretic peptide (ANP) was only stimulatory in epithelial cells. [125I] CNP bound specifically to mesangial cells with a Kd of 0.47 nM and Bmax of 42 fmol/mg. Equilibrium of binding was obtained after four to five hours at +4 degrees C and nonspecific binding represented 10 to 20% of total binding. HS142-1 (100 micrograms/ml), a specific inhibitor of ANPR-A and ANPR-B, suppressed 90% of CNP-dependent cyclic GMP production whereas it had little effect on [125I]-CNP binding, suggesting that C receptors were largely predominant in mesangial cells. No biological effect of CNP on mesangial cells, including change in basal or angiotensin II-induced contractility and inhibition of basal or serum-dependent proliferation, could be demonstrated. Similar results were obtained with 8-bromo-cyclic GMP and sodium nitroprusside. Intraglomerular localization of ANPR-A, ANPR-B and ANPR-C mRNA was studied using reverse transcriptase-polymerase chain reaction with amplification of their corresponding cDNA by different primers. Amplification products were identified on gel electrophoresis by their predicted sizes and sequencing. ANPR-A, ANPR-B and ANPR-C mRNA were present in epithelial cells whereas only ANPR-B and ANPR-C mRNA were detected in mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1994

Angiotensin II receptors and renin release in rat glomerular afferent arterioles.

The purpose of recent studies was to investigate the expression of angiotensin II (Ang II) receptor sites in afferent arterioles freshly isolated from the rat kidney, and the role of Ang II on renin release by these vessels. The method of isolation and purification of renal microvessels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with the aid of a magnetic field, successive passages through various sieves, and harvesting with collagenase. Ang II receptor characteristics were evaluated by radioligand binding studies using the non-peptide Ang II antagonists of AT1 (Dup-753 and -532) and AT2 (PD-123319 and CGP-42112) receptors. AT1 antagonists displaced up to 80% of the Ang II binding with high affinity (3 nM), whereas the remaining 20% showed low affinity for the Dup compounds and CGP-42112 (> 10 microM), and intermediate affinity for PD-123319 (12 microM). These data suggest the existence of two Ang II receptor subtypes in the renal vasculature of the rat. In separate experiments, renin release by isolated afferent arterioles in vitro was 9 ng/hr/mg under control conditions. Ang II (0.1 microM) inhibited renin secretion by 20%, whereas the adenylyl cyclase activator forskolin (10 microM) stimulated renin secretion by 50%. In arterioles isolated from rats chronically treated with a converting enzyme inhibitor (perindoprilate) to reduce endogenous formation of Ang II, renin release increased 20-fold under control conditions in vitro and was further stimulated by forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Plasma atrial and brain natriuretic peptides in mitral stenosis treated by valvulotomy.

1. In order to appreciate the effect of changes in left atrial pressure on plasma brain natriuretic peptide, 20 patients with mitral stenosis treated by percutaneous valvulotomy were studied 10 min before and 15 min after the first balloon inflation. They were also studied 24 h before and 48 h after the valvulotomy. At these times the effect of postural changes on brain natriuretic peptide secretion was examined. A group of 10 control subjects was also studied under basal conditions. In each case, plasma atrial natriuretic peptide was measured in parallel with plasma brain natriuretic peptide. 2. Similarly to plasma atrial natriuretic peptide, plasma brain natriuretic peptide was elevated in patients with mitral stenosis (32 +/- 2.9 and 32 +/- 2.8 pg/ml in the upright and supine position respectively versus 13.5 +/- 0.5 and 13.8 +/- 1.8 pg/ml in controls; P < 0.01). Changing from standing to lying did not modify plasma brain natriuretic peptide, whereas it produced an increase in plasma atrial natriuretic peptide in controls (13.3 +/- 1.6 versus 24.8 +/- 5.2 pg/ml; P < 0.01) and in patients 48 h after valvulotomy (52.5 +/- 4.6 versus 66.9 +/- 6.6 pg/ml; P < 0.01). Plasma brain natriuretic peptide also fell at this time (18.8 +/- 1.1 and 19.1 +/- 1.1 pg/ml in the upright and supine position respectively; P < 0.01) similarly to plasma atrial natriuretic peptide and cyclic GMP (P < 0.01). The acute left atrial mean pressure variation was significantly correlated with the parallel change in plasma atrial natriuretic peptide (P < 0.001) but not in plasma brain natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Differential regulation of angiotensin II and losartan binding sites in glomeruli and mesangial cells.

The aim of the present report was to examine the effect of several agents on angiotensin II (ANG II) and losartan receptors using 125I-[Sar1,Ala8]ANG II and [3H]losartan as radiolabeled ligand, respectively. ANG II receptors were downregulated in glomeruli from rats infused with ANG II during 3 wk or rats receiving losartan orally during 1 wk. The number of sites (Bmax) was reduced, but the dissociation constant (Kd) value was unchanged. Losartan receptors were downregulated in glomeruli from rats receiving losartan, but remained unchanged in glomeruli from rats infused with ANG II. Since in vivo administration of losartan results in increase of plasma ANG II and formation of metabolites, in vitro studies using human mesangial cells were performed to better analyze the present findings. Treatment of mesangial cells during 4 days by ANG II, losartan, or its metabolite, EXP-3174, also produced downregulation of 125I-[Sar1,Ala8]ANG II binding sites with a decreased Bmax and unchanged Kd value. Only treatment of mesangial cells by ANG II or EXP-3174 produced downregulation of [3H]losartan binding sites. In contrast, exposure of these cells to losartan resulted in upregulation of [3H]losartan binding sites. Under all conditions, only Bmax was modified. Whereas internalization of [3H]losartan in mesangial cells was negligible under all experimental conditions, there was an increase of the percentage of internalized 125I-[Sar1,Ala8]ANG II after exposure of the cells to ANG II or AT1 antagonists. No change was observed in mesangial cell AT1 receptor mRNA levels. This study demonstrates that 1) AT1 mRNA is expressed in human mesangial cells; 2) the characteristics of 125I-[Sar1,Ala8]ANG II and [3H]losartan binding sites in rat glomeruli and human mesangial cells are different, with Kd and Bmax values greater in both preparations when [3H]losartan was utilized; 3) both types of binding sites obey different regulations, and the effects of losartan in vivo are due in part to the associated increase in plasma ANG II levels and the transformation of the drug into its metabolite, EXP-3174; 4) downregulation of AT1 receptors does not depend on changes in mRNA expression but is associated with increased relative internalization.

Administration, Oral↗
PubMed1994

Plasma atrial natriuretic factor and blood pressure drops during hemodialysis.

The potential role of atrial natriuretic factor (ANF) in blood pressure (BP) drops during hemodialysis (HD) has been examined in 30 patients with end-stage chronic renal failure. Echocardiographic measurements and evaluation of cardiac parasympathetic function were performed prior to HD sessions, simultaneously with hormonal determinations. The plasma ANF level was correlated with the peak value of the E wave and the Doppler index of the left ventricular preload and was more elevated in 'denervated' than in intact patients. During the HD sessions, the BP fell in 18 patients (group 1) and remained stable in 12 others (group 2), despite similar weight losses. Both groups differed by the basal values of plasma ANF, greater in group 1 than in group 2 (100.0 +/- 13.3 vs. 65.7 +/- 3.4 fmol/ml; p < 0.05). The magnitude of plasma ANF decrease was identical in both groups despite the BP decrease in group 1 at the end of the session. These results suggest that the ANF release depends not only on hemodynamics but also on cardiac innervation in dialyzed patients and that high plasma ANF levels are implied in the BP drops during HD session.

Adult↗
PubMed1993

Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy.

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Characterization of [3H]losartan receptors in isolated rat glomeruli.

[3H]Losartan bound specifically to isolated rat glomeruli. Scatchard analysis revealed a single class of losartan binding sites with an apparent dissociation constant (KD) of 6.2 nM and a density of receptor sites (Bmax) of 1.2 pmol/mg protein. In comparison, [3H][Sar1,Ala8]angiotensin II binding sites exhibited the same KD value (4.3 nM), but a considerably lower Bmax (52 fmol/mg protein). Moreover whereas [125I][Sar1,Ala8]angiotensin II was almost equally displaced by angiotensin II, [Sar1,Ala8] angiotensin II and losartan, [3H]losartan was potently displaced by losartan only. Finally, [125I][Sar1,Ala8]angiotensin II but not [3H]losartan binding sites were sensitive to guanosine triphosphate (GTP) gamma S and Dithiothreitol. These data, together with the recent demonstration of intrinsic effects of losartan, support the view that [3H]losartan does not label only the angiotensin II type 1 receptor (AT1).

Animals↗