UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The role of nitric oxide (NO) in leukocyte (polymorphonuclear cells, monocytes and lymphocytes) emigration was studied in a model of carrageenin-sponge implants in rats. 2. The subcutaneous implantation of 1% (w/v) of lambda-carrageenin-soaked sponges elicited an inflammatory response that was characterized by a time-related increase in leukocyte infiltration in the sponges and increased levels of nitrite in the exudate. Total leukocyte infiltration and nitrite production were maximal at 24 h and decreased after 48 and 96 h. The mononuclear cell influx was maximal at 48 h (21% of the total leukocytes). Therefore, this time point was used in the successive experiments. 3. Polymorphonuclear cell (PMN) and lymphocyte infiltration in the sponges significantly increased when rats were treated with the non-specific NO-synthase (NOS) inhibitor, NG-nitro-L-arginine methylester (L-NAME) (1 mg ml-1) in drinking water ad libitum). Monocyte emigration was not affected by L-NAME treatment. The nitrite levels in the exudate of L-NAME-treated rats were significantly reduced. The concomitant ingestion of L-arginine (30 mg ml-1) resulted in a reversion of the L-NAME effect, while D-arginine (30 mg ml-1) had no effect, indicating the involvement of the L-arginine: NO pathway. 4. Administration of L-NAME resulted also in an increased release of tumour necrosis factor-alpha (TNF-alpha) and prostacyclin (measured as the stable metabolite, 6-keto-PGF 1 alpha). L-NAME had no effect on monocyte chemoattractant protein-1 (MCP-1) release in the exudate. 5. Since L-NAME may have effects on the local blood flow, phenylephrine (0.034 mg ml-2) in drinking water) was used as it has an effect on the local blood flow similar to L-NAME. Phenylephrine had no effect on either leukocyte emigration, or on nitrite, TNF-alpha, prostacyclin or MCP-1 accumulation in the exudate. 6. In contrast, the more selective iNOS inhibitor S-methyl-isothiourea (SMT) (10 micrograms ml-1) in drinking water) significantly reduced PMNs and lymphocyte influx in the sponge having no effect on monocyte influx. Moreover, SMT decreased nitrite production in the exudate to a comparable extent as L-NAME. 7. Administration of SMT significantly reduced MCP-1 release in the exudate, without an effect on TNF-alpha or prostacyclin production. Moreover SMT did not produce any changes in local blood flow. 8. Our results show that a different outcome of the inflammatory process can be obtained depending on the types of NOS inhibitor used.
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PMID:Differential effect of L-NAME and S-methyl-isothiourea on leukocyte emigration in carrageenin-soaked sponge implants in rat. 928 97

1. The pulmonary vasculature is normally in a low resting state of tone. It has been hypothesized that this basal tone is actively maintained by the continuous release of a vasodilator in the resting state. However, evidence for basal release of nitric oxide (NO) is inconclusive. 2. We studied the release of NO in arteries from the pulmonary circulation of male Wistar-Kyoto rats by examining the effects of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME) on resting pulmonary arteries and on vessels pre-contracted with prostaglandin F2(alpha) (PGF2 alpha). 3. Rats (n = 21) were killed by an overdose with pentobarbitone. Pulmonary arteries were dissected (mean internal diameter 459 +/- 11 microns) and mounted in a small vessel wire myograph. Resting tensions were to set to stimulate transmural pressures of 17.5 mmHg. 4. L-NAME (100 microM) was found to produce a contraction of 0.64 +/- 0.09 mN mm-1 in resting pulmonary arteries when added alone to the myograph bath. This contraction was not produced following removal of the endothelium. Vessel contraction to PGF(2 alpha) (100 microM) was found to be significantly greater when carried out in the presence of L-NAME (100 microM) -1.37 +/- 0.15 mN mm-1 compared with 1.96 +/- 0.17 mN mm-1. Dilation following acetylcholine (ACh) (1 microM) was abolished in the presence of L-NAME (100 microM). 5. Rat pulmonary artery contraction in response to the addition of L-NAME and the absence of contraction upon removal of the endothelium provides supportive evidence of the active release of nitric oxide for the maintenance of resting tone.
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PMID:Response of normoxic pulmonary arteries of the rat in the resting and contracted state to NO synthase blockade. 929 34

We examined the presence and the regulation of nitric oxide (NO) synthase (NOS) using in vitro cultured corpora lutea (CL) obtained from rabbits at days 4 and 9 of pseudopregnancy. The role of NO and NOS on steroidogenesis was also investigated using the same CL preparations after short-term incubations (30 min and 2 h) with the NO donor, sodium nitroprusside (NP), the NOS inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME) and prostaglandin (PG) F-2alpha. The basal NOS activity was greater in CL at day 4 than at day 9, and was also differently modulated by PGF-2alpha, depending on the age of the CL. The addition of PGF-2alpha to day 4 CL had no effect, but PGF-2alpha on day 9 caused a threefold increase in NOS activity. NP caused a two- to fivefold decrease in release of progesterone from CL of both ages, and this inhibitory effect on steroidogenesis was reversed by l-NAME. All treatments failed to modify basal androgens and 17beta-oestradiol was not detectable in either control or treated CL. These results suggest that NO is effectively involved in the regulation process of steroidogenesis, independently of 17beta-oestradiol. PGF-2alpha had no effect on day 4, but induced luteolysis on day 9, by reducing progesterone (P</=0. 01) to about 18% of control. The luteolytic action of PGF-2alpha was completely reversed by co-incubation with l-NAME, thus supporting the hypothesis that luteolysis is mediated by NO. The addition of NP or l-NAME did not modify the in vitro release of PGF-2alpha. We hypothesised that PGF-2alpha upregulates NOS activity and, consequently, the production of NO, which acutely inhibits progesterone release from day 9 CL of pseudopregnant rabbits.
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PMID:Nitric oxide synthase acutely regulates progesterone production by in vitro cultured rabbit corpora lutea. 992 97

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

Nitric oxide (NO) may normally impair endothelin (ET) activity in epicardial coronary arteries. Lifting this inhibitory feedback could reveal ET-dependent effects involving ET(A)- and/or ET(B)-receptor activation. In conscious dogs, the blockade of ET(A) receptors (intracoronary Ro-61-1790) increased external circumflex coronary artery diameter (CD) (sonomicrometry) by 0.10 +/- 0.01 from 3.04 +/- 0.12 mm (P < 0.01) without altering coronary blood flow (Doppler). Similarly, CD increased (0.09 +/- 0.01 from 2.91 +/- 0.14 mm; P < 0. 01) when Ro-61-1790 was given after blockade of NO formation with intracoronary N(omega)-nitro-L-arginine methyl ester (L-NAME). In contrast, ET(B)-receptor blockade (intracoronary Ro-46-8443) did not influence baseline CD with and without L-NAME. In vitro, increases in tension caused by N(omega)-nitro-L-arginine (L-NNA) or PGF(2alpha) in arterial rings were reduced by ET(A)- but not ET(B)-receptor blockade. ET(A)-receptor blockade also reduced the increase in tension caused by L-NNA in human coronary arterial rings. Thus ET(A) receptors, but not ET(B) receptors, account for ET-dependent constriction in canine epicardial coronary arteries in vivo. ET-dependent effects were independent of the level of NO formation in vitro and in vivo. In human epicardial coronary arterial rings, ET(A)-receptor blockade also caused significant relaxation.
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PMID:Contribution of endogenous endothelin to large epicardial coronary artery tone in dogs and humans. 1044 77

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

Tumor necrosis factor alpha (TNFalpha) has been shown to be a potent stimulator of prostaglandin (PG) F(2alpha) secretion in the bovine endometrium. The aims of the present study were to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGF(2alpha) in response to TNFalpha, and the intracellular mechanisms of TNFalpha action. Cultured bovine epithelial and stromal cells were exposed to TNFalpha (0.006-6 nM) or oxytocin (100 nM) for 4 h. TNFalpha resulted in a dose-dependent increase of PGF(2alpha) production in the stromal cells (P < 0.001) but not in the epithelial cells. On the other hand, oxytocin stimulated PGF(2alpha) output in the epithelial cells but not in the stromal cells. When the stromal cells were incubated for 24 h with TNFalpha and inhibitors of phospholipase (PL) C or PLA(2), only PLA(2) inhibitor completely stopped the actions of TNFalpha (P < 0.001). When the stromal cells were exposed to TNFalpha and arachidonic acid, the action of TNFalpha was augmented (P < 0.001). When the stromal cells were incubated for 24 h with a nitric oxide (NO) donor (S-NAP), S-NAP stimulated the PGF(2alpha) production dose-dependently. Although an NO synthase (NOS) inhibitor (L-NAME) reduced TNFalpha-stimulated PGF(2alpha) production, an inhibitor of phosphodiesterase augmented the actions of TNFalpha and S-NAP (P < 0. 05). The overall results indicate that the target of TNFalpha for stimulation of PGF(2alpha) production in cattle is the endometrial stromal cells, and that the actions of TNFalpha are mediated via the activation of PLA(2) and arachidonic acid conversion. Moreover, TNFalpha may exert a stimulatory effect on PGF(2alpha) production via the induction of NOS and the subsequent NO-cGMP formation.
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PMID:Production of prostaglandin f(2alpha) by cultured bovine endometrial cells in response to tumor necrosis factor alpha: cell type specificity and intracellular mechanisms. 1077 56

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F(2alpha)(PGF(2alpha)) (1-100 micrometer). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, >/=450 mmHg and </=50 mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21+/-3.6 to 28.3+/-2.6 mmHg; (P</= 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0. 3-3000 p m) caused a concentration dependent reduction of the PGF(2alpha)induced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P</= 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-omega-arginine methyl ester (l -NAME, 1-100 micrometer), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P</= 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controls. In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.
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PMID:Fetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension. 1098 75

1. The NO-dependent component of cyclic AMP-induced vasorelaxation in rat pulmonary arteries is critically dependent on extracellular L-arginine but independent of endothelial cell intracellular [Ca(2+)]. We examined whether L-arginine uptake was also essential for NO production induced by passive stretch or isometric tension, processes also reported to be Ca(2+)-independent. 2. The passive length-tension curve was depressed by physiological concentrations of L-arginine (400 microM; P<0.05). Inhibition of the y(+) transporter with 10 mM L-lysine, NO synthase with L-NAME (100 microM), or protein tyrosine kinase with erbstatin A (30 microM) caused identical upward shifts (P<0.001), alone or in combination. Tyrphostin 23 was similar to erbstatin A, whilst the inactive analogue tyrphostin A1 and genistein were without effect. 3. L-arginine (400 microM) shifted the PGF(2 alpha) concentration-response curve under isometric conditions to the right (P<0.05), whereas L-NAME or L-lysine caused a leftward shift (P<0.001). Tyrphostin 23 (30 microM) more than reversed the L-arginine-induced suppression of PGF(2 alpha)-induced tension; subsequent addition of L-NAME had no effect. The L-lysine-sensitive component of CPT cyclic AMP-induced vasorelaxation was abolished by erbstatin A. 4. ACh-induced vasorelaxation was approximately 80% inhibited by L-NAME, but was not affected by L-lysine or 400 microM L-arginine. Erbstatin A reduced the vasorelaxation by only approximately 25%. 5. We conclude that activation of NO production by stretch, isometric tension, or cyclic AMP in rat pulmonary arteries is critically dependent on the presence and uptake of physiological concentrations of extracellular L-arginine, and protein tyrosine kinase activity. This directly contrasts with ACh-induced vasorelaxation, which was independent of extracellular L-arginine, and relatively unaffected by tyrosine kinase inhibition.
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PMID:Essential role of L-arginine uptake and protein tyrosine kinase activity for NO-dependent vasorelaxation induced by stretch, isometric tension and cyclic AMP in rat pulmonary arteries. 1109 Jan 23

The present study investigated the effect of nitric oxide (NO) on the lifespan of the corpus luteum (CL). Using a competitive nitric oxide synthase (NOS) inhibitor, L-nitro arginine methyl ester (L-NAME, 600 micromol/l), and a long-life NO donor, diethyl-aminetriamine (DETA-NONOate, 10(-8), 10(-6) or 10(-4) mol/l), we found that in ovaries from rats at the mid stage of CL development, endogenous NO increased both glutathione (GSH) and progesterone production. However, during prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis NO acted as an intermediary molecule in the inhibitory effect of PGF(2 alpha), on GSH content. This was supported by the fact that in-vivo PGF(2 alpha) treatment enhanced nitric oxide synthase (NOS) activity. These results indicate that the NO could act with a dual action (protective or pro-oxidant) in CL development.
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PMID:Dual effects of nitric oxide in functional and regressing rat corpus luteum. 1113 59

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