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Biomedical subjects

L Sautebin

Publications and source records attributed to L Sautebin.

At least 37 records · Page 2Linked to original sources
PubMed1997

The role of constitutive and inducible nitric oxide synthase in senna- and cascara-induced diarrhoea in the rat.

The role of constitutive and inducible nitric oxide (NO) synthase in rats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca(2+)-dependent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascara, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara-(but not senna-) induced diarrhoea and colonic fluid secretion. These findings suggest that senna probably exerts its laxative effect through stimulation of the constitutive isoform of NO synthase, while the inducible isoform of NO synthase also seems to be involved in the laxative effect of cascara.

Administration, Oral↗
PubMed1997

Effect of methylguanidine, guanidine and structurally related compounds on constitutive and inducible nitric oxide synthase activity.

The inhibitory activity of methylguanidine, guanidine and their precursors, creatine and creatinine, on both the neuronal constitutive and lung inducible isoforms of nitric oxide synthase were examined in this study. Methylguanidine and guanidine (0.01-3 mM) significantly (P<0.01) inhibited in a concentration-dependent manner both isoforms of the enzyme. Furthermore analysis of the inhibition curves by ANOVA revealed that methylguanidine and guanidine act as non selective inhibitors of both nitric oxide synthases (P>0.4 for both methylguanidine and guanidine). In contrast, creatine and creatinine, although containing guanidine group, were totally ineffective on either enzyme even at concentration up to 3 mM. The results obtained for tested compounds also suggest a role for the lateral chain of guanidine group in the enzyme inhibition. The lack of selectivity of methylguanidine and guanidine in inhibiting both the nitric oxide synthase enzymes could account for some pathological manifestations like neurological disorders, host defense impairment and probably hypertension, that often occur in patients with uremia or chronic renal failure.

Animals↗
PubMed1997

Multiple organ failure following zymosan-induced peritonitis is mediated by nitric oxide.

In the present study we tested the hypothesis that nitric oxide may play a role in the pathogenesis of multiple organ failure induced by peritoneal injection of zymosan in the rat. A severe inflammatory response characterized by peritoneal exudation, high plasma and peritoneal levels of nitrate/ nitrite (breakdown products of nitric oxide), prostaglandin E2 and leukocyte infiltration into peritoneal exudate was induced by zymosan administration. This inflammatory process started within 3 h of administration and onset occurred at 18 h, coinciding with damage of lung, small intestine and liver, as assessed by histological examination and by increase of myeloperoxidase activity, indicative of neutrophil infiltration. Furthermore, at 18 h after zymosan-induced peritonitis, expression of inducible nitric oxide synthase enzyme was found mainly in the macrophages of inflamed lungs. Subcutaneously administration of a nonisoform selective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced formation of peritoneal exudate fluid, blocked plasma and peritoneal nitrate/nitrite accumulation, and attenuated the elevated release of peritoneal prostaglandin E2. In addition, nitric oxide synthase inhibition was effective in preventing the development of organ failure since tissue injury and neutrophil infiltration, by myeloperoxidase evaluation, was reduced in lung, small intestine, and liver. In conclusion, major findings of our study are that nitric oxide exerts a proinflammatory role in the development of multiple organ failure and nitric oxide synthase inhibition is an effective antiinflammatory therapeutic tool, since inhibits not only nitric oxide but also prostaglandin production and cellular infiltration in inflamed organs.

Acute Disease↗
PubMed1996

Inhibition of nitric oxide formation reduces voluntary ethanol consumption in the rat.

Brain nitric oxide is involved in the mechanisms that regulate ingestive behavior. To test whether this compound plays a role in alcohol preference, we studied the effects of different doses of NG-nitro-L-arginine (L-NO arg), an inhibitor of nitric oxide synthase (NOS), on voluntary consumption of ethanol and on blood alcohol levels produced by a single intraperitoneal dose of alcohol in the rat. L-NO arg produced a significant and dose-dependent reduction of ethanol intake (P < 0.001) without influencing total fluid consumption or feeding behavior. L-NO arg did not influence the kinetics of alcohol. Our data show that inhibition of nitric oxide formation accompanies reduction of ethanol intake and suggest a possible role for nitric oxide in ethanol self-administration.

Alcohol Drinking↗
PubMed1995

Endogenous nitric oxide increases prostaglandin biosynthesis in carrageenin rat paw oedema.

The influence of endogenous nitric oxide (NO) on prostaglandin biosynthesis in rat carrageenin oedema was studied. Oedema formation and prostaglandin E2 generation in the inflamed paw were both increased by L- but not D-arginine and reduced by the NO synthase inhibitor, L-NG-nitro arginine methyl ester, and the NO scavenger, haemoglobin. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. These results suggest that endogenous NO modulates carrageenin oedema by increasing prostaglandin biosynthesis at the inflammatory site through a cGMP-independent mechanism.

Animals↗
PubMed1995

Modulation by nitric oxide of prostaglandin biosynthesis in the rat.

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw). 6. In LPS-treated rats (6 mg kg-1, i.p.) doses of AA inactive in normal animals produced a remarkable oedema which was reduced by L-NAME or Hb, unaffected by Mb and increased by L-arginine.7. These results demonstrate that NO increases prostaglandin biosynthesis in vivo through a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-independent mechanism and suggest that the interaction between NO synthase and cyclo-oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Nitric oxide modulates prostacyclin biosynthesis in the lung of endotoxin-treated rats.

In this study we have investigated the correlation between prostaglandin generation and the L-arginine:nitric oxide (NO) pathway in the lung of rats challenged with lipopolysaccharide. We found that in rats treated with L-arginine, the amount of prostacyclin, measured as 6-keto-PGF1 alpha, was significantly increased. Conversely in rats treated with NG-nitro-L-arginine methyl ester the production of 6-keto-PGF1 alpha by lung was significantly decreased. Chopped lungs that had been removed from rats challenged with lipopolysaccharide and were incubated overnight with L-arginine or nitric oxide inhibitors, NG-nitro-L-arginine methyl ester or NG-monomethyl-L-arginine, released respectively increased or decreased amount of 6-keto-PGF1 alpha. These results suggest that, in the rat, lung endogenous nitric oxide may modulate prostanoid production.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Food deprivation increases brain nitric oxide synthase and depresses brain serotonin levels in rats.

We studied nitric oxide (NO) synthase activity and serotonin content in the diencephalon of 24 hr food deprived rats. NO synthase activity was significantly increased whereas serotonin levels together with those of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO synthase, was used as a tool to study the role of NO in food deprivation. Twenty-four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.) administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr after food presentation. L-NO Arg administration produced a dose-dependent reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it increased serotonin levels. Our data indicate that NO might have a physiological role in the regulation of food intake and suggest that brain NO may modulate the central serotoninergic system.

Amino Acid Oxidoreductases↗
PubMed1992

Lipocortin and vasocortin: two species of anti-inflammatory proteins mimicking the effects of glucocorticoids.

The anti-inflammatory effect of glucocorticoids depends, at least in part, on the induction of two regulatory proteins, lipocortin and vasocortin, both preventing the release of inflammatory mediators. Lipocortin inhibits phospholipase A2 (PLA2) and therefore reduces arachidonic acid metabolites formation. Vasocortin inhibits histamine release from mast cells. Lipocortin and vasocortin may be regarded as the first two identified members of the (perhaps greater) family of glucocorticoid-induced proteins.

Animals↗
PubMed1992

Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774.

The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids.

Amino Acid Oxidoreductases↗
PubMed1989

Vasocortin-like proteins induced by glucocorticoids in vascular tissue.

Rat and bovine aorta rings incubated with 10(-5) M dexamethasone release proteins which inhibit rat dextran oedema. These proteins seem to be related to vasocortin, derived from the peritoneal fluid of dexamethasone-treated rats, and may contribute to the control that glucocorticoids exert on vascular tonus and permeability.

Adrenalectomy↗
PubMed1989

Selective inhibition by vasocortin of histamine release induced by dextran and concanavalin-A from rat peritoneal cells.

Vasocortin, a glucocorticoid-induced anti-inflammatory protein, has been purified from the peritoneal lavage fluid of dexamethasone-treated rats. Vasocortin inhibited the release of histamine from rat peritoneal cells stimulated by dextran or concanavalin A but did not alter the release induced by calcium ionophore A23187 or compound 48/80. This selective effect exhibited by vasocortin mimics the glucocorticoid inhibition of histamine release from rat mast cells.

Animals↗
PubMed1987

Vasocortin: a novel glucocorticoid-induced anti-inflammatory protein.

The preliminary characterization of ;vasocortin' a novel glucocorticoid-induced anti-inflammatory protein, is described. Vasocortin is released into the rat peritoneal cavity following systemic dexamethasone administration, has an apparent mol. wt. of 100 kD and inhibits rat dextran oedema. Vasocortin is distinct from lipocortin and is likely to be associated with the anti-inflammatory effect of glucocorticoids.

Animals↗
PubMed1986

Effect of the beta-2 adrenergic agonist fenoterol on the release of leukotrienes and prostaglandin D2 from human lung parenchyma.

Ca++-ionophore and antigen challenge of human lung fragments caused a massive release of leukotrienes, whose relative proportions varied considerably and were dependent on the experimental conditions. A broncho-selective beta 2-adrenoceptor agonist fenoterol was able to prevent the antigen-induced leukotriene release completely, whereas the Ca++-ionophore induced leukotriene release was only moderately inhibited. The HPLC data were confirmed by SRS-A bioassay.

Arachidonic Acid↗
PubMed1986

Stimulus-related difference in the formation of leukotrienes and PGD2 after immunological and non-immunological challenge of human lung parenchyma "in vitro".

The stimulation of human lung parenchymal fragments with A-23187 induces formation of leukotrienes as well as of PGD2: LTE4 is the compound found in larger amount and independently of the intensity of the stimulus the % of metabolized precursor which is converted to leukotrienes or PGD2 is remarkably similar. However, under conditions of IgE-Anti IgE challenge the predominant conversion of arachidonic acid occurs to PGD2, LTB4 is almost negligible and LTD4 and E4 together represent less than 30% of the oxidative products of arachidonic acid. Whether PGD2 and leukotrienes derive from the same or different subset of cells is unresolved.

Antibodies↗