Induction of nitric oxide synthase by lipoteichoic acid from <i>Staphylococcus aureus</i> in vascular smooth muscle cells

Auguet, Michel; Lonchampt, Marie-Odile; Delaflotte, Sylvie; Goulinschulz, J; Chabrier, P; Braquet, P.

doi:10.1016/0014-5793(92)80356-l

Cited by 65 publications

(34 citation statements)

References 12 publications

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“…Under these conditions, a loss of contraction tonicity to PE (10 pM) was observed. This phenomenon has previously been attributed to the induction of NOS (11)(12)(13)(14). The drugs were added after 60 min of PE-induced contraction when the contractile impairment was maximal.…”

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confidence: 91%

Selective Inhibition of Inducible Nitric Oxide Synthase by Agmatine

Auguet¹,

Viossat²,

Marin³

et al. 1995

Japanese Journal of Pharmacology

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135

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ABSTRACT-Agmatine was about as potent as aminoguanidine to inhibit the activity of the inducible form of nitric oxide synthase (iNOS) in isolated rat aorta. Like aminoguanidine, agmatine was devoid of significant activity on the constitutive form of NOS. Agmatine inhibited the conversion of [3H]L-arginine in [3H]L-citrulline in partially purified iNOS from macrophages (IC50=262±39.9 pM). Thus, our data suggest that agmatine may act as endogenous inhibitor of iNOS.Keywords: Agmatine, Nitric oxide, Inducible enzyme L-Arginine is a nutritionally semiessential amino acid involved in a variety of physiological processes (1). Arginine plays a role in protein and creatine biosynthesis and, as an intermediate in the urea cycle, is converted to ornithine by arginase. However, other enzymes that catalyze the conversion of arginine have been identified. In this respect, nitric oxide synthase (NOS) produces the potent vasodilator nitric oxide (NO) (2, 3), and arginine decarboxylase converts arginine to agmatine (4). This latter enzyme, orginally observed in bacteria, has been recently found in mammalian brain (5). In addition, agmatine was identified as an endogenous clonidine-displacing substance (5). Thus, it was hypothesized that arginine may have an antihypertensive effect through NO and agmatine formation by NOS and arginine decarboxylase, respectively (6). However, Pinthong et al. (7) showed that despite recognition at a2-adrenoceptor binding sites, agmatine failed to produce functional a2-adrenoceptor activity not only in the isolated guinea pig ileum but also in other functional models of a2-adrenoceptors. In this respect, agmatine failed to mimic the effect of clonidine in isolated rat vas deferens or isolated porcine palmar lateral vein. In addition, in rat cerebral cortex, agmatine produced a concentrationdependent inhibition of 3H-clonidine, but failed, unlike UK-14304, to inhibit forskolin-stimulated cyclic AMP. Thus collectively, the results indicate that agmatine may not posses sufficient a2-adrenoceptor agonist properties to influence cardiovascular function as recently observed (8). Although a possible role of agmatine as a substrate for NOS has been ruled out (9), other guanidines such as aminoguanidine may act against NO formation (10).Thus, the aim of this study was to test the possible interaction of agmatine with NO synthesis. Thoracic aortae were excised from male Sprague Dawley rats (270-360g;Charles River, Paris, France). Rings, 2-mm-wide, were suspended (2 g tension) in organ baths containing 20 ml of Krebs-Henseleit solution (for composition see below) at 371C and gassed with 95% 02 /5% CO2. After a 1-hr rest period, contractile responses were measured using force-displacement transducers connected to a data collection system (IOS; Dei Leirre, Mitry Mory, France). Physiological solution was composed of: 118 mM NaCl, 4.7 mM KC1, 2.5 mM CaC12, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO3 and 11 mM glucose.In a first series of experiments, rings possessing a functional endothelium were precontracted wit...

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confidence: 91%

Selective Inhibition of Inducible Nitric Oxide Synthase by Agmatine

Auguet¹,

Viossat²,

Marin³

et al. 1995

Japanese Journal of Pharmacology

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135

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“…In contrast to endotoxic shock, we know relatively little about the mechanisms by which Gram-positive bacteria, which lack endotoxin, cause shock and MODS. However, lipoteichoic acid (LTA) from Staphylococcus aureus causes the induction of a calciumindependent isoform of nitric oxide (NO) synthase (iNOS) in vascular smooth muscle cells and macrophages in vitro and the signal transduction pathway leading to the expression of iNOS by LTA in cultured macrophages (J774.2) involves the activation of tyrosine kinase and the nuclear transcription factor NFKB (Auguet et al, 1992;Cunha et al, 1993;De Kimpe et al, 1995a;Kengatharan et al, 1996a). Staphylococcus aureus LTA causes circulatory failure as well the induction of iNOS protein and activity in the rat lung (De Kimpe et al, 1995a).…”

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide in the circulatory failure and organ injury in a rodent model of Gram‐positive shock

Kengatharan

Kimpe

Thiemermann

1996

British J Pharmacology

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1 The pathological features of Gram-positive shock can be mimicked by the co-administration of two cell wall components of Staphylococcus aureus, namely lipoteichoic acid (LTA) and peptidoglycan (PepG). This is associated with the expression of the inducible isoform of nitric oxide synthase (iNOS) in various organs. We have investigated the effects of dexamethasone (which prevents the expression of iNOS protein) or aminoguanidine (an inhibitor of iNOS activity) on haemodynamics, multiple organ dysfunction syndrome (MODS) as well as iNOS activity elicited by LTA+PepG in anaesthetized rats. 2 Co-administration of LTA (3 mg kg-', i.v.) and PepG (10 mg kg-', i.v.) resulted in a significant increase in the plasma levels of tumour necrosis factor-a (TNFa, maximum at 90 min) as well as a biphasic fall in mean arterial blood pressure (MAP) from 120 + 3 mmHg (time 0) to 77 + 5 mmHg (at 6 h, n = 8; P< 0.05). This hypotension was associated with a significant tachycardia (4-6 h, P <0.05) and a reduction of the pressor response elicited by noradrenaline (NA, 1 mg kg-', i.v., at 1-6 h; n =8, P < 0.05). Furthermore, LTA + PepG caused time-dependent increases in the serum levels of markers of hepatocellular injury, glutamate-pyruvate-transaminase (GPT) and glutamate-oxalacetate-transaminase (GOT). In addition, urea and creatinine (indicators of renal dysfunction) were increased. There was also a fall in arterial oxygen tension (Pao2), indicating respiratory dysfunction, and metabolic acidosis as shown by the significant drop in pH, Paco2 and HCO3-. These effects caused by LTA + PepG were associated with the induction of iNOS activity in aorta, liver, kidney and lungs as well as increases in serum levels of nitrite + nitrate (total nitrite). 3 Pretreatment of rats with dexamethasone (3 mg kg-', i.p.) at 120 min before LTA + PepG administration significantly attenuated these adverse effects as well as the increases in the plasma levels of TNFa caused by LTA + PepG. The protective effects of dexamethasone were associated with a prevention of the increase in iNOS activity (in aorta, liver, lung, kidney), the expression of iNOS protein (in lungs), as well as in the increase in the plasma levels of total nitrite. 4 Treatment of rats with aminoguanidine (5 mg kg-' + 10 mg kg-h-) starting at 120 min after LTA + PepG attenuated most of the adverse effects and gave a significant inhibition of iNOS activity (in various organs) as well as an inhibition of the increase in total plasma nitrite. However, aminoguanidine did not improve renal function although this agent caused a substantial inhibition of NOS activity in the kidney. 5 Thus, an enhanced formation of NO by iNOS importantly contributes to the circulatory failure, hepatocellular injury, respiratory dysfunction and the metabolic acidosis, but not the renal failure, caused by LTA + PepG in the anaesthetized rat.

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“…However, intravenous infusions of GBS and other Gram-positive bacteria cause pulmonary haemodynamic and gas exchange abnormalities similar to those observed in LPS-injected animals (Rojas et Author for correspondence. Schreiber et al, 1992) suggesting a common pathway leading to these abnormalities (Auguet et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Group B Streptococcus and E. coli LPS‐induced NO‐dependent hyporesponsiveness to noradrenaline in isolated intrapulmonary arteries of neonatal piglets

Villamor

Pérez‐Vizcaíno

Ruiz

et al. 1995

British J Pharmacology

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The effects of endotoxin (E. coli lipopolysaccharide, LPS) and heat inactivated group B Streptococcus (GBS) were studied on the contractile responses to noradrenaline (NA) in isolated pulmonary arteries and on the activity of the constitutive and inducible nitric oxide synthase (NOS) in lung fragments of neonatal piglets. Short‐term (≤ 5 h) incubation with LPS (1 μg ml−1) or GBS (3 × 107 colonies forming units ml−1) did not modify the vascular responsiveness to NA (10−8 M‐10−4 m) in isolated intrapulmonary arteries. However, long‐term incubation (20 h) with LPS or GBS produced a significant reduction in the maximal contractile responses and shifted the concentration‐response curve for NA downwards. Endothelium removal or the cyclo‐oxygenase inhibitor meclofenamate (10−5 m) did not affect the GBS‐ and LPS‐induced hyporesponsiveness to NA. The presence of the nitric oxide (NO) precursor, l‐arginine (10−5 m), 30 min prior to the contractility challenge increased the LPS‐ and GBS‐induced pulmonary vascular hyporesponsiveness to NA. In contrast, the addition, prior to the challenge with NA, of the NOS inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME, 10−4m) or coincubation with dexamethasone (3 × 10−6m), a potent inhibitor of the induction of NOS, or with the protein synthesis inhibitor cycloheximide (10−5 m) completely restored the reactivity to NA in LPS‐ and GBS‐treated pulmonary arteries. The incubation for 20 h of lung fragments with LPS and GBS produced a significant increase in the Ca2+‐independent (inducible) NOS activity determined by the conversion of radiolabelled l‐arginine to citrulline, but did not modify the constitutive NOS activity. This NOS induction was abolished by coincubation with dexamethasone (3 × 10−6 m). These results demonstrated that prolonged incubation with GBS and LPS causes an induction of NOS activity which results in a reduced vascular responsiveness to NA in pulmonary arteries of neonatal piglets. Thus, induction of NOS seems to be responsible for the delayed pulmonary vascular hyporesponsiveness induced by GBS (a Gram‐positive) and E. coli (a Gram‐negative), the most common causal agents of neonatal sepsis.

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Induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells

Cited by 65 publications

References 12 publications

Selective Inhibition of Inducible Nitric Oxide Synthase by Agmatine

Selective Inhibition of Inducible Nitric Oxide Synthase by Agmatine

Role of nitric oxide in the circulatory failure and organ injury in a rodent model of Gram‐positive shock

Group B Streptococcus and E. coli LPS‐induced NO‐dependent hyporesponsiveness to noradrenaline in isolated intrapulmonary arteries of neonatal piglets

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