Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Oedema formation in skin is dependent on a synergism between mediators that increase vascular permeability and mediators that enhance local blood flow. Leukocyte accumulation is also enhanced by mediators that increase local blood flow. In this study, we have investigated whether nitric oxide (NO), an important endogenous vasodilator, could modulate oedema formation and leukocyte accumulation in guinea-pig skin. 2. Local administration of the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), dose-dependently inhibited the oedema formation induced in response to intrademal injection of bradykinin or histamine. L-NAME, but not NG-nitro-D-arginine methyl ester (D-NAME); also inhibited oedema formation in response to i.d. injection of platelet-activating factor (PAF), zymosan-activated plasma (ZAP) and in a passive cutaneous anaphylactic (PCA) reaction. 3. N-iminoethyl-L-ornithine (L-NIO) was less effective and about 100 times less potent than L-NAME in inhibiting bradykinin-induced oedema formation. The cyclo-oxygenase inhibitor, ibuprofen, had little effect on oedema responses induced by bradykinin, PAF and in a PCA reaction. On the other hand, histamine-induced oedema formation was significantly suppressed by ibuprofen. 4. The inhibition by L-NAME of bradykinin-induced oedema formation was reversed by co-injection of sodium nitroprusside (SNP) or prostaglandin E1 (PGE1). 5. L-NAME inhibited 111In-eosinophil and 111In-neutrophil accumulation induced by i.d. injection of ZAP. 111In-eosinophil accumulation induced by PAF and in the PCA reaction was also inhibited by L-NAME but not by D-NAME. 6. Co-injection of SNP or PGE1, reversed the inhibition by L-NAME of ZAP-induced oedema formation and 111In-neutrophil accumulation. SNP, but not PGE1, also reversed the effects of L-NAME on ZAP-induced 111In-eosinophil accumulation.7. L-NAME caused a significant decrease in basal cutaneous blood flow when injected alone or with bradykinin. Again, SNP or PGE, reversed the effects of L-NAME suggesting that the inhibitory action of L-NAME on oedema formation and cell accumulation was due to an inhibition of vasodilator tone in the microcirculation.8. Thus, it appears that in guinea-pig skin the inhibition of the production of endogenous NO inhibits both leukocyte accumulation and oedema formation induced by different mediators of inflammation.Since administration of L-NAME also causes a local decrease in basal blood flow, we suggest that this is the mechanism by which it exerts anti-inflammatory effects in this model.
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PMID:Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea-pig skin. 830 95

We recently reported that intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli. In the present study, we examined the effect of the PGE receptor EP1 subtype antagonist ONO-NT-012, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the allodynia. The PGE2-induced allodynia was blocked by simultaneous i.t. injection of ONO-NT-012, MK-801, or L-NAME. However, 5 min after i.t. injection of PGE2, the allodynia was significantly blocked by i.t. L-NAME, but not by i.t. ONO-NT-012 or MK-801. These results demonstrate that the PGE2-induced allodynia, once developed, does not require the continued agonist occupancy of EP1 and NMDA glutamate receptor sites.
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PMID:L-NAME, an inhibitor of nitric oxide synthase, blocks the established allodynia induced by intrathecal administration of prostaglandin E2. 878 49

Embryonic implantation is a complex process in which both maternal and embryonic signals are involved. In the present study, we evaluated changes in uterine prostaglandins production and nitric oxide synthase (NOS) activity during the course of early pregnancy and their interaction during implantation in rats. Uterine phospholipase A2 (PLA2) activity is increased on days 5 (day of ovoimplantation) and 6, compared to preimplantation days (3 and 4). This enhanced activity might be responsible for the observed increase in uterine PGE and PGF2 alpha production observed on day 5 of pregnancy, which induces endometrial vascular permeability and decidualization. When embryo access to the uterus is impaired, the increase of PG production is suppressed. During postimplantation, PGE levels return to preimplantation values, while PGF2 alpha decreased with respect to preimplantation values. Uterine NOS activity is also increased on day 4 and reaches a maximum on day 5, with a profile similar to PGE and PGF2 alpha. Dexamethasone administered in vivo decreased uterine NOS activity on day 4 of pregnancy but not on day 5, suggesting the presence of at least two types of NOS enzymes in the early days of pregnancy. A competitive inhibitor of NOS, L-NAME (600 and 1000 microM) induced a decrease in PGE and PGF2 alpha production in uterine tissue on day 5 of pregnancy. These results suggest the existence of a physiologically relevant nitridergic system which modulates prostaglandin production in the rat uterus during embryonic implantation.
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PMID:Interaction between uterine PGE and PGF2 alpha production and the nitridergic system during embryonic implantation in the rat. 887 32

Smooth muscle myometrial cells isolated by an enzymatic method from estrogenized rats were used after 7-10 days of culture. They were incubated for 24 h with two distinct competitive nitric oxide (NO) inhibitors: NG-monomethyl-L-arginine (L-NMMA: 300 microM) and L-nitro-arginine methylester (L-NAME: 600 microM, 5 mM and 10 mM). Afterwards, the supernatants were separated in order to measure nitrite production and prostaglandin PGE synthesis. In the present report, we demonstrate that myometrial cells from estrogenized rats are able to produce NO, since all the inhibitors significantly decrease the production of nitrites in the culture media. Furthermore, we report that both inhibitors inhibited PGE synthesis by myometrial cells. We also used a donor of NO in the incubation medium for 24 h, sodium nitroprusside (NP), obtaining an strong (P< 0.001) increase in both nitrite and PGE production. We conclude that myometrial cells can produce NO and that one possible role of the NO synthetized by this cells may be the modulation of PGE production.
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PMID:Regulation of prostaglandin production by nitric oxide in rat smooth muscle myometrial cells. 1031 20

Granuloma reaction around Schistosoma mansoni eggs is the prominent lesion in human schistosomiasis. Studies have suggested the involvement of a series of suppressive mechanisms in the control of this reaction. Using an in vitro model of granuloma formation, we have shown that immune complexes (IC) isolated from sera of chronic intestinal schistosomiasis patients were able to reduce granulomatous reaction developed against soluble egg antigen-conjugated polyacrylamide beads. In this system, the role of the l-arginine-nitric oxide (NO) pathway in the formation of prostaglandin E(2) (PGE(2)) by human peripheral blood mononuclear cells (PBMC) of patients infected with schistosomiasis was investigated using IC. Preincubation of PBMC with IC produced a significant increase of both nitrite and PGE(2) levels in the cell supernatant. This effect was inhibited by coincubation of cells with Nomega-nitro-l-arginine methyl ester (L-NAME), a NO synthase inhibitor, showing that the release of PGE(2) subsequent to IC stimulation was driven by NO. The inhibitory effect of L-NAME on PGE(2) release by IC-treated PBMC was reversed by sodium nitroprusside, a known NO donor. Our results indicate that NO could be an important second signal for the stimulation of PGE(2) production induced by IC in PBMC from human schistosomiasis patients.
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PMID:Nitric oxide-mediated immune complex-induced prostaglandin E(2) production by peripheral blood mononuclear cells of humans infected with Schistosoma mansoni. 1043 95

Nitric oxide (NO) is synthesized by the rat ovary and a role in the follicular development, the ovulation, and the luteal formation has been postulated. The aims this study were to determine the activity of nitric oxide synthase (NOs) enzyme during the ovulatory process and to demonstrate the existence of a relationship between the ovarian NO production and the synthesis of prostaglandins (PGs) involved in the follicular rupture. Prepuberal rats treated with PMSG/hCG to induce ovulation were used. The NOs activity, measured by [(14)C]citrulline formation, showed an increase after PMSG administration and reached a maximum at 10 h after hCG injection. NOs activity remained high up to 24 h post ovulation. At 10 h after the hCG injection, the activity of Ca(2+)-dependent NOs (constitutive NOs) was similar to that seen at 0 h, and the activity of Ca(2+)-independent NOs (inducible NOs) increased from 14.4 to 51% of total activity. The in vitro ovarian production of PGE and PGF(2alpha) was inhibited by L-NAME and stimulated by 3-morpho-linosydnonimine (SIN-1), a NO donor. The in vivo production of ovarian prostaglandins was also inhibited by the intrabursal administration of two NOs inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA). Our results suggest that the inducible NOs (iNOs) is the main isoform involved in the ovulatory process and that the NO produced stimulates the synthesis of both PGE and PGF(2alpha) from the cyclooxygenase pathway, to enhance the process of follicle rupture.
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PMID:Activity of ovarian nitric oxide synthase (NOs) during ovulatory process in the rat: relationship with prostaglandins (PGs) production. 1044 73

In the corpus luteum (CL), prostaglandin F(2alpha) (PGF(2alpha)) is a physiological agent with luteolytic actions. Nitric oxide (NO) is a messenger molecule capable of modulating diverse pathophysiological processes. The aim of the present study was to investigate the role of ovarian NO in PGE (a luteotrophic prostanoid) and PGF(2alpha) (a luteolytic prostanoid) production and in progesterone synthesis during CL regression in the rat. To obtain a longer functional CL, we used a pseudopregnant (PSP) rat model. By means of intrabursa ovarian sac treatment of two competitive nitric oxide synthase (NOS) inhibitors, N(G)-monomethyl-L-arginine (L-NMMA, 1 mg/kg) and N(W)-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg), and sodium nitroprusside (SNP, 0.05 mg/kg) as a NO generator, we found that NO, produced by the ovarian tissue during the last 2 days of CL development (days 8 and 9), increased PGF(2alpha) production in the ovary and diminished serum progesterone concentrations leading to CL involution. We also proposed a positive feedback mechanism between PGF(2alpha) and NO, to ensure luteal regression. Thus, we injected intraperitoneally a luteolytic dose (3 microg/kg) of a synthetic PGF(2alpha) during the mid and late phase of CL development. Ovarian NOS activity was evaluated. The results confirmed our hypothesis; we did not see any effect in the mid-stage of CL development, but increased ovarian NOS activity was found in PGF(2alpha)-injected late pseudopregnant rats.
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PMID:The involvement of nitric oxide in corpus luteum regression in the rat: feedback mechanism between prostaglandin F(2alpha) and nitric oxide. 1054 62

Our previous study has demonstrated the potentiation by uridine triphosphate (UTP) of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated murine J774 macrophages. In this study, we found that the amount of interleukin-6 (IL-6) release in response to LPS stimulation was greatly enhanced in the presence of UTP. This enhancement exhibited concentration dependence and occurred after 8 h of treatment with LPS. RT-PCR analysis indicated that the steady-state level of IL-6 mRNA induced by LPS was apparently increased upon co-addition of UTP. The potentiation by UTP was inhibited by the treatment with U73122 (a phosphatidylinositol-phospholipase C inhibitor), BAPTA/AM (an intracellular Ca(2+) chelator), KN-93 (a selective inhibitor of calmodulin-dependent protein kinase) or PDTC (a nuclear factor kappaB inhibitor). To understand the cross-regulation among NO, PGE(2) and IL-6, all of which are dramatically induced after LPS stimulation, the effects of L-NAME (a nitric oxide synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), NS-398 (a cycloxygenase-2 inhibitor) and IL-6 antibody were tested. The results revealed the positive regulation between PGE(2) and IL-6 synthesis because NS-398 and indomethacin inhibited LPS plus UTP-induced IL-6 release, and IL-6 antibody attenuated LPS plus UTP-induced PGE(2) release. Taken together these results reinforce the role of UTP as a regulatory element in inflamed sites by demonstrating the capacity of this nucleotide to potentiate LPS-induced release of inflammatory mediators.
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PMID:Potentiation of lipopolysaccharide-induced IL-6 release by uridine triphosphate in macrophages: cross-interaction with cyclooxygenase-2-dependent prostaglandin E(2) production. 1054 78

The purpose of this study was to investigate the in vivo effects of intracavernosal injections of galanin and galantide (a specific galanin receptor antagonist) on penile erection in the anesthetized cat. Erectile responses to galanin and galantide were compared with responses to a standard triple drug combination [1.65 mg papaverine, 25 microg phentolamine, and 0.5 microg prostaglandin E(1) (PGE(1))]. Intracavernosal injections of galanin (3-100 nmol) and galantide (0. 1-3 nmol) induced penile erection in a dose-dependent manner. In terms of relative potency, galantide was approximately 100-fold more potent than galanin at increasing cavernosal pressure. The maximal increases in intracavernosal pressure in response to galanin and galantide were 83 and 95%, respectively, of the control triple drug combination. The total durations of erectile response caused by these peptides were significantly shorter (P<0.05) than those by the triple drug combination. The nitric oxide synthase inhibitor L-NAME (20 mg) significantly decreased the erectile response in the cat to galantide but not to galanin, while the K(+)(ATP) channel antagonist U-37883A (3 mg) had no effect on the erectile response to galanin nor galantide. The results of the present study demonstrate that galantide, a putative antagonist for the galanin receptor, has more potent agonist activity than galanin in increasing intracavernosal pressure in the cat. Moreover, these data suggest that galantide, but not galanin, causes penile erection by an NO/cGMP-dependent mechanism. This is the first study to demonstrate that galanin may play a role in the physiology of penile erection.
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PMID:Nitric oxide-mediated erectile effects of galantide but not galanin in vivo. 1083 89

We tested the effects of 11 commercially-available isoprostanes on platelet aggregation directly or when triggered by the thromboxane receptor agonist U46619 or collagen in healthy human citrated blood using a whole blood aggregometer. None of the isoprostanes tested triggered aggregation alone, nor facilitated aggregation by a sub-threshold dose of U46619 or collagen. Five isoprostanes inhibited aggregation (rank order of potency 8-iso PGE(1)>8-iso PGE(2)>8-iso PGF(2alpha)>8-iso PGF(3alpha)>8-iso-13,14-dihydro-15-keto PGF(2alpha)). Blood incubated with LPS to induce a gross inflammatory response exhibited a time dependent (2 - 12 h) reduction in aggregation to U46619 but maintained a consistent response to collagen. Under these conditions, as in control blood, none of the isoprostanes tested induced aggregation. In fact, the inhibitory actions of isoprostanes on U46619-induced aggregation were enhanced in blood treated with LPS. L-NAME inhibited aggregation induced by U46619 in fresh blood and in blood treated with LPS. In the presence of L-NAME, (with or without LPS) none of the isoprostanes tested induced aggregation but retained their inhibitory action. Thus, in human whole blood the action of 8-iso PGE(1), 8-iso PGE(2), 8-iso PGF(2alpha), 8-iso PGF(3alpha), and 8-iso-13,14-dihydro-15-keto PGF(2alpha) is antiaggregatory. Moreover, this inhibitory capacity is still apparent and may be enhanced in blood subjected to inflammatory stimulation.
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PMID:Characterization of the effects of isoprostanes on platelet aggregation in human whole blood. 1130 41


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