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R Ardaillou

Publications and source records attributed to R Ardaillou.

At least 91 records · Page 5Linked to original sources
PubMed1991

Cyclic adenosine monophosphate-stimulating agents induce ecto-5'-nucleotidase activity and inhibit DNA synthesis in rat cultured mesangial cells.

The ecto-5'-nucleotidase activity of rat glomerular mesangial cells increases after exposure to prostaglandin E2 (PGE2) via cAMP stimulation (Savic et al., 1990, Immunology 70, 321). Therefore we examined whether other cAMP-stimulating agents had a similar effect. Forskolin (1 microM), PGE2 (10 microM), and isoproterenol (10 microM), three products stimulating rat mesangial cell adenylate cyclase activity, enhanced cAMP accumulation within 5 min and 5'-nucleotidase activity after a lag time of at least 24 h, 3-Isobutyl-1-methylxanthine (IBMX) and Ro 20-1724, two drugs inhibiting cAMP degradation, also stimulated cAMP accumulation and 5'-nucleotidase activity. The effects of these agents on 5'-nucleotidase activity were additive with those of the three products stimulating adenylate cyclase activity, except for Ro 20-1724 and forskolin which acted synergistically. Cycloheximide, a blocker of protein synthesis, suppressed the cAMP-dependent increase of 5'-nucleotidase activity. Because ecto-5'-nucleotidase activity is a marker of cell differentiation, the effect of the same cAMP-stimulating agents on cell proliferation was also studied. Forskolin, PGE2, and isoproterenol inhibited [3H]thymidine incorporation into rat mesangial cells in a dose-dependent manner. The same effect was obtained with IBMX (100 microM) and Ro 20-1724 (50 microM). Stimulation of 5'-nucleotidase activity and inhibition of [3H]thymidine incorporation occurred over the same range of concentrations for the various agonists tested. Taken together, these results indicate that expression of ecto-5'-nucleotidase in rat mesangial cells is induced by cAMP whatever the reason for its accumulation. The simultaneous inhibition of DNA synthesis may occur independently or be associated with the stimulation of 5'-nucleotidase expression.

5'-Nucleotidase↗
PubMed1991

Desferrioxamine regulates tumor necrosis factor release in mesangial cells.

Cultured rat mesangial cells have been demonstrated to express tumor necrosis factor alpha (TNF alpha) mRNA and to release TNF activity into the medium upon stimulation by bacterial lipopolysaccharide (LPS). The present study was undertaken to determine whether TNF was only secreted by mesangial cells or was also present as a cell-associated molecule. LPS-activated mesangial cells which had been fixed in paraformaldehyde lysed the TNF-sensitive L-929 fibroblasts, as assessed by 51Cr release. This cytotoxic activity was inhibited by anti-TNF alpha antiserum. Cell-associated TNF expression was demonstrable after less than one hour of exposure to LPS, peaked at two hours and decreased progressively thereafter, while TNF activity increased in the medium. Mesangial cell-associated TNF was localized at the cell surface, as shown by immunohistochemical demonstration and by the ability of plasma membranes purified from LPS-activated mesangial cells to lyse L-929 fibroblasts. Flow cytometry experiments revealed that two-thirds of LPS-activated mesangial cells were stained by anti-TNF alpha antiserum. The major part of these cell-associated TNF molecules persisted after low pH treatment, indicating that they were integral membrane proteins. As assessed by immunoprecipitation analysis, these proteins were 26 kDa molecules, whereas the released forms of TNF were 17 kDa molecules. Pretreatment of mesangial cells with desferrioxamine (DFX), an iron chelator preventing the synthesis of hydroxyl radicals (OH.), delayed the release of TNF from the membranes into the medium, and enhanced its cell surface expression. It also subsequently accelerated its decay in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Characterization of ANF receptors in cultured renal cortical vascular smooth muscle cells.

Because atrial natriuretic factor (ANF) has been demonstrated to decrease resistances in cortical renal vessels in vivo, we studied 125I-ANF binding and ANF-dependent guanosine 3',5'-cyclic monophosphate (cGMP) production in subcultured vascular smooth muscle cells (VSMC) prepared from the rabbit renal cortex. 125I-ANF specific binding at 4 degrees C represented 70% of total binding and reached a plateau at 30-60 min. Equilibrium saturation binding curves suggested one group of high-affinity receptor sites (KD = 78 +/- 16 pM, Bmax = 45 +/- 11 fmol/mg) but were compatible with several groups exhibiting close binding parameters. ANF, [Ala7,Ala23]ANF (a linear analogue), and C-ANF-(4-23) (a ligand of C receptors) inhibited 125I-ANF binding at 37 degrees C with nearly similar potencies. In contrast, at 4 degrees C, complete or nearly complete inhibition of binding was obtained with ANF and linear ANF, the latter exhibiting the weakest potency, whereas C-ANF-(4-23) displaced only 35% of the tracer. ANF markedly stimulated cGMP accumulation, with a threshold concentration of 10 pM and a stimulation of 115 times basal value at 0.1 microM. Linear ANF was also stimulatory with a much weaker potency. Around 25% of 125I-ANF bound to cell surface was internalized at 37 degrees C. Phenylarsine oxide partially inhibited internalization as well as the inhibitory potency of C-ANF-(4-23) on 125I-ANF binding. As shown by high-performance liquid chromatography extracellular 125I-ANF was rapidly degraded at 37 degrees C into its 125I-COOH-terminal tripeptide and 125I-Tyr.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1991

Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites.

We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites.

Administration, Oral↗
PubMed1990

Nordihydroguaiaretic acid inhibits urokinase synthesis by phorbol myristate acetate-stimulated LLC-PK1 cells.

Protein kinase C (PKC) activation is regulated by Ca2+, phospholipids, diacylglycerol (DAG) and fatty acids. Phorbol myristate acetate (PMA) which mimics the effect of DAG on PKC induces transcriptional activation of the urokinase-type plasminogen activator (u-PA) gene in LLC-PK1 cells. We examined in the present work the relationships between PKC activity, fatty acids, and u-PA synthesis in this cell line. We showed that H7, an inhibitor of PKC, inhibited the PMA-induced u-PA synthesis by LLC-PK1 cells. PMA-induced u-PA synthesis was enhanced by eicosatetraynoic acid (ETYA), a competitive inhibitor of both the lipoxygenase and cyclooxygenase pathways and inhibited by nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway. Three other unrelated lipoxygenase inhibitors (phenidone 100 microM, BW755 50 microM and diethylcarbamazine 50 microM) had no effect on u-PA biosynthesis. Two polyunsaturated fatty acids other than ETYA, arachidonic acid and linoleic acid, also potentiated the PMA effect and a lipoxygenase derivative, 12 hydroxyeicosatetraenoic acid (12 HETE), did not modify the basal and PMA-stimulated u-PA syntheses. PKC activity purified from cytosol of LLC-PK1 cells was stimulated by addition of 16 nM PMA in vitro and this effect was blunted by simultaneous addition of 5 microM NDGA. By Northern blot analysis using a pig u-PA cDNA probe we found that PMA increased the steady state level of u-PA mRNA after 2 h of incubation and that NDGA inhibited this effect. These data suggest that NDGA inhibits PMA-stimulated PKC activity in intact cells leading to a decrease of u-PA mRNA level and u-PA biosynthesis in PMA-stimulated LLC-PK1 cells. Polyunsaturated fatty acids have opposite effects.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Effect of plasma volume expansion on hemodynamics and atrial natriuretic factor release in heart-transplant recipients.

Plasma atrial natriuretic factor (ANF), plasma cyclic guanosine monophosphate (cGMP), plasma aldosterone, plasma-renin activity (PRA) and hemodynamic parameters were measured in heart-transplant recipients and control patients (chest pain syndrome) during right-sided heart catheterization under basal conditions and in response to an intravenous saline load. Basal plasma ANF and cGMP were higher in heart-transplant recipients than in control patients, whereas PRA and plasma aldosterone did not differ. The high plasma ANF levels in heart-transplant recipients did not result from high atrial pressures but appeared to be related with elevated atrial dimensions and cyclosporine-induced renal failure. During volume expansion, plasma ANF increased in control patients and remained elevated during the postinfusion period. In heart-transplant recipients, the changes in plasma ANF were less marked despite identical increases of atrial pressures. The sluggish response of plasma ANF in this group was associated in the postinfusion period with a nonreturn of the hemodynamic parameters to their basal values in contrast with what was observed in control patients.

Adult↗
PubMed1990

Reduction in tumor necrosis factor binding and cytotoxicity by hydrogen peroxide.

The regulatory effect of H2O2 on both the cytotoxic activity and the specific binding of TNF-alpha was studied by using TNF-alpha-sensitized murine L929 cells. When these cells were exposed simultaneously to TNF-alpha and H2O2 (100 to 500 microM), the cytotoxic activity of TNF-alpha was inhibited by up to 66.6%. This inhibition was also effective when the cells were pretreated by H2O2, but not when TNF-alpha alone was preexposed to H2O2. These data suggest that H2O2 altered the cell sensitivity to TNF-alpha, without modifying the activity of the TNF-alpha molecule. Maximum loss of cell sensitivity to TNF-alpha occurred after 30-min preexposure to 500 microM H2O2. Complete restoration of TNF-alpha sensitivity was obtained within 12 h after H2O2 removal. It required protein synthesis as demonstrated by the suppressive effect of actinomycin D. The inhibitory effect of H2O2 was suppressed by catalase, but was unaffected by the scavengers of hydroxyl radical and hypochlorous acid, suggesting that H2O2 but not one of its metabolites was responsible for this inhibition. H2O2 inhibitory effect did not implicate any change in prostaglandin production or in PKC activity. In contrast, H2O2 effect was associated with an about 50% loss of the density of cell membrane 125I-TNF-alpha receptors (2949 vs 5620 binding sites per cell), without change in their affinity (3.9 vs 3.4 nM). Moreover H2O2 did not affect the rate of degradation of TNF-alpha, and only slightly increased the degree of internalization of 125I-TNF-alpha receptors. These findings indicate that H2O2 can down-regulate the cellular response to TNF-alpha, possibly by reducing the TNF-alpha-binding capacity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.

We compared the relative potencies of sinorphan and retorphan, the S- and R-enantiomers of acetorphan a potent inhibitor of enkephalinase (EC 3.4.34.11), to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration. In mice, sinorphan was 2-3 fold as potent as retorphan in inhibiting the specific in vivo binding of [3H]acetorphan to kidney enkephalinase. The same potency ratio was found for the enhancement of trichloroacetic acid-precipitated radioactivity in kidneys of mice that had received 125I-ANF, which is used as a test for the protection of the hormone against inactivation in vivo. In nine healthy human volunteers who had received a low oral dosage of sinorphan or retorphan in a double-blind, placebo-controlled, randomized trial, sinorphan was also 2-3 fold more potent than retorphan in inhibiting plasma enkephalinase activity. These effects were accompanied by a related rise in plasma ANF immunoreactivity, which also reflected the difference in the effectiveness of the two compounds. Sinorphan was also more potent than retorphan in enhancing urinary cyclic GMP excretion and sodium excretion in five of these subjects. These data indicate that, in humans as in rodents, enkephalinase plays a crucial role in the inactivation of ANF, its partial inhibition in vivo being accompanied by a significant protection of the exogenous or endogenous hormone as well as by typical ANF-like responses. Thus orally administered sinorphan appears to be a promising compound for therapeutic use in cardiovascular and renal diseases in which ANF has been postulated to exert beneficial effects.

Administration, Oral↗
PubMed1990

Effect of prostaglandin E2 on proline uptake and protein synthesis by cultured human mesangial cells.

PGE2 production by glomeruli is increased in a variety of glomerular diseases. Potentially, this process may affect mesangial cell protein synthesis and mesangial cell growth. Thus studies have been undertaken, using cultured human mesangial cells, to assess the effects of PGE2 on proline uptake, protein synthesis and cell proliferation. In the presence of 140 mM NaCl, incubation of mesangial cells with 0.01 to 1 microM PGE2 for 72 hours resulted in a marked decrease of 14C proline uptake, but did not modify 14C leucine uptake. Substitution of choline to sodium inhibited 14C proline uptake by 85% which became independent of PGE2, indicating that this PG specifically altered sodium-dependent proline uptake. Inhibition of this component reached 35 to 50% with 1 microM PGE2. The inhibitory effect of PGE2 on sodium-dependent proline uptake required a lag time of 48 hours, and was suppressed by ouabain, an inhibitor of Na+, K+ ATPase activity. PGE2 did not modify the Vmax of the transport system (1.007 vs. 1.023 nmol/mg/min) but increased (P less than 0.01) its Km (1.179 vs. 0.823 mM). 8-bromo-cyclic AMP also inhibited sodium-independent proline uptake, and PGE2 markedly increased cyclic AMP production. Taken together, these results suggested that PGE2 acted via cyclic AMP stimulation. PGE2 under identical conditions (1 microM, 72 hr incubation) produced a decrease in collagen synthesis estimated by the relative rate of collagen production after incubation of mesangial cells with 14C proline (percentage of 14C radioactivity in collagenase-sensitive proteins over total proteins). PGE2 also diminished the intracellular free proline pool. More generally, PGE2 inhibited cell proliferation and cell total proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1990

Atrial natriuretic factor and changes in dietary sodium intake in patients with chronic renal failure.

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively. 2. There was a parallel decrease from 6.31 +/- 0.75 to 2.17 +/- 0.32% in the fractional excretion of filtered sodium and from 234.4 +/- 74.9 to 80.6 +/- 20.3 pg/ml (supine position) or 140.1 +/- 43.6 to 60.7 +/- 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P less than 0.05). The ratio of plasma guanosine 3':5'-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium. 3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Atrial natriuretic peptide response to postural changes in patients with left atrial hypertension.

Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (GMP) and renin activity (PRA) were measured in 13 patients with mitral stenosis 24 h before and 48 h after balloon valvotomy resulting in a fall in LA pressure from 23.4 +/- 2.2 to 10.5 +/- 0.8 mmHg (P less than 0.01). Before treatment, plasma ANP was higher during ambulation (128.1 +/- 18.5 pg ml-1) than in the supine posture (93.3 +/- 15.0 pg ml-1; P less than 0.01) and did not diminish after return to the erect posture (86.4 +/- 14.1 pg ml-1). A physiological response was restored after valvotomy with ANP plasma levels of 49.2 +/- 7.8 pg ml-1 in the initial ambulant period, 63.1 +/- 12.6 pg ml-1 in the supine posture and 44.6 +/- 8.7 pg ml-1 in the final erect posture. Postural variations of cyclic GMP were parallel to those of ANP. In contrast, LA hypertension did not abolish PRA postural response. During the three successive periods of ambulation, supine posture and erect posture PRA was 5.4 +/- 1.0, 2.8 +/- 0.6 and 5.5 +/- 1.2 ng h-1 ml-1, respectively, before treatment, whereas after treatment the values measured were 10.3 +/- 2.9, 2.3 +/- 0.7 and 7.0 +/- 2.5 ng h-1 ml-1 respectively. Variations of plasma ANP, cyclic GMP and PRA in response to postural changes were also studied in 10 healthy volunteers and in 12 uraemic patients with high plasma ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

In vitro production of tumour necrosis factor and prostaglandin E2 by peripheral blood mononuclear cells from tuberculosis patients.

We investigated the production of tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) from tuberculosis patients and healthy controls. PBMC from tuberculosis patients generated constitutively more TNF-alpha than did control PBMC. This production was significantly higher for patients with high-grade fever and cachexia. The increase of TNF-alpha production by PBMC from tuberculosis patients was associated with a comparatively weaker elevation of PGE2 synthesis which did not parallel fever or weight loss. In vitro treatment of control PBMC with the tuberculin purified protein derivative (PPD) promoted an increased TNF-alpha production which was similar to that of untreated PBMC from tuberculosis patients. Thus, the increased TNF-alpha production in tuberculosis could be explained by the in vivo exposure of PBMC to mycobacterial antigens. In contrast, the concentration of PGE2 was weaker in the medium of untreated PBMC from tuberculosis patients than in the medium of PPD-treated control PBMC, suggesting that PGE2 synthesis by PBMC was limited in tuberculosis by unidentified factors.

Adult↗
PubMed1990

Characterization of atrial natriuretic factor receptors in human glomerular epithelial and mesangial cells.

To evaluate the distribution and functions of receptors of atrial natriuretic factor (ANF) in human glomeruli, we studied the binding sites of ANF-(1-28) in homogeneous populations of human glomerular epithelial cells or mesangial cells. 125I-labeled ANF bound specifically to both cell types. Equilibrium saturation binding curves suggested one group of receptor sites in mesangial cells (Kd = 99 +/- 32 pmol/l, Bmax = 15.3 +/- 3.5 fmol/mg) but multiple groups in glomerular epithelial cells. Binding was greater at 37 than at 4 degrees C in mesangial cells. The reverse was observed in glomerular epithelial cells due to marked degradation of the tracer at 37 degrees C. The fractions of undisplaceable tracer in a hypertonic acid medium after 60 min incubation were 45 and 16% at 37 degrees C for glomerular epithelial and mesangial cells, respectively. ANF-(1-28) and C-ANF-(4-23), a specific ligand of clearance receptors, similarly inhibited 125I-ANF binding to mesangial cells, whereas [Ala7-Ala23]-ANF, a linear analogue, was slightly less potent. In epithelial cells, C-ANF-(4-23) competitively inhibited 125I-ANF binding but with a lower potency than ANF, whereas linear ANF at low concentrations (10-100 pmol/l) stimulated 125I-ANF binding. In addition, linear ANF markedly inhibited the degradation of 125I-ANF in the incubation medium of epithelial and mesangial cells, whereas thiorphan, an inhibitor of enkephalinase, was inactive. ANF-(1-28) stimulated cGMP production in glomerular epithelial cells but not in mesangial cells. Both analogues were inactive in both cell types and did not modify ANF-(1-28)-dependent cGMP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1990

Current indications of plasma atrial natriuretic peptide measurements in human diseases.

The discovery of atrial natriuretic peptide (ANP) has modified our current understanding of the regulation of sodium metabolism. This peptide, of which the second messenger is cyclic guanosine monophosphate (cyclic GMP), is released by the atrial myocytes in response to increased atrial stretch and has for essential function to diminish the venous return to the heart. Radioimmunoassays have demonstrated that plasma ANP and cyclic GMP levels are increased in various diseases such as congestive heart failure (CHF), renal insufficiency, and, to a lesser extent, diabetes mellitus and liver cirrhosis with ascites. Plasma ANP is of prognostic value in CHF and reflects the effective central volemia in renal failure so that its assay as well as that of plasma cyclic GMP seem of interest in these diseases. Further studies are needed to assess the pathophysiological significance of ANP in diabetes mellitus and cirrhosis, and to define the indications of the treatment by enkephalinase inhibitors which increase endogenous ANP levels by lowering the catabolism of this hormone.

Acute Kidney Injury↗
PubMed1990

Induction of ecto-5'-nucleotidase of rat cultured mesangial cells by interleukin-1 beta and tumour necrosis factor-alpha.

Because ecto-5'-nucleotidase activity of rat glomerular mesangial cells has been shown to increase upon interaction with macrophages in vitro, it was examined whether interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha), two macrophage-released cytokines, were responsible for this effect. IL-1 beta and TNF-alpha stimulated mesangial cell 5'-nucleotidase activity in a dose-dependent manner after treatment for 24 hr. Maximum increases reached 4.5 times and 1.7 times basal values for IL-1 beta (20 U/ml) and TNF-alpha (25 ng/ml), respectively. The effects of both cytokines were additive. Stimulation of 5'-nucleotidase by IL-1 beta and TNF-alpha was specific since the activity of other ectoenzymes, such as Mg2(+)-ATPase, was unchanged. Cycloheximide, a blocker of protein synthesis, suppressed the cytokine-dependent increase of 5'-nucleotidase activity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen inhibited approximately 50% of the effects of both cytokines. Their inhibitory effect was abolished in the presence of prostaglandin E2 (PGE2). In addition, PGE2 itself produced a dose-related (0.1-10 microM) increase of 5'-nucleotidase activity with a maximum of 2.2 times basal value. Taken together, these results indicate that IL-1 beta, essentially, and TNF-alpha, to a lesser extent, regulate 5'-nucleotidase expression in the plasma membrane of cultured mesangial cells and that their effect depends in part on PGE2 synthesis. Therefore, macrophages, via their products of secretion acting on 5'-nucleotidase, could modulate adenosine production in the glomerular capillaries.

5'-Nucleotidase↗
PubMed1989

Effects of bradykinin on prostaglandin synthesis and cytosolic calcium in rabbit subcultured renal cortical smooth muscle cells.

Smooth muscle cells were cultured from an arteriole-rich fraction of the rabbit renal cortex and characterized by their ultrastructural and immunohistochemical features, their high content in creatine kinase (60-times that of the initial preparation) and their ability to synthesize renin. Cells, studied between passages 2 and 5, produced mainly PGE2 and, to a lesser extent, PGF2 alpha. Bradykinin (BK) (0.1 nM-1 microM) induced a concentration-dependent increase in PGE2 (28-40-times basal value at 1 microM after a 5 min incubation period) and stimulated also the free cytosolic calcium concentration [( Ca2+]i) with a 2-fold maximal rise to its basal value. Both effects, inhibited by the anti-B2 receptor [Thi5.8D-Phe7] BK, were not reproduced by DesArg9 BK. A decrease in the extracellular calcium concentration and incubation in the presence of a calcium-channel blocker (lanthanum chloride) inhibited the BK-dependent rise of [Ca2+]i but not that of PGE2. Preincubation with phorbol myristate acetate increased basal and BK-induced PGE2 synthesis but prevented the effect of BK on [Ca2+]i. These results demonstrate the ability of BK to increase [Ca2+]i and PGE2 production in cultured vascular cells from the rabbit renal cortex and suggest that kinins might act on the cortical microcirculation via their direct effects on arteriolar smooth muscle cells.

Animals↗