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

Uterine secretory cells receive a sympathetic cholinergic secremotor innervation. Nitric oxide (NO) has been suggested to be a second messenger of neurogenic modulated glandular secretion of the seminal vesicle. Thus a similar pattern for nervous induced carbohydrate secretion of the endometrium was assumed. The nitric oxide synthase (NOS) activity was estimated via formation of L-citrulline from L-arginine and histochemically with the nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) nitro blue technique. The carbohydrate secretion from everted uterine horns placed in organ baths was estimated. A calcium dependent formation of citrulline was found in the uterine horn suggesting an NOS activity. Strong NADPH staining cells were found in the glandular ducts of the endometrium and in the epithelial linings of the oviduct. Carbachol induced carbohydrate secretion of the endometrium while N-nitro L-arginin (L-NNA) and N-nitro L-arginin methyl ester (L-NAME) inhibited the carbachol induced secretion. The isomer D-NAME had no effect on carbachol induced secretion. When L-arginine was administered together with L-NNA no inhibitory effect on carbachol induced secretion was seen. L-arginine only had no effect on carbohydrate secretion. The NO donor glyceryl tritrate increased carbohydrate secretion but no synergistic effect was seen in combination with carbachol. The results suggest that glandular NO production is a prerequisite for muscarinic carbohydrate secretion of the endometrium.
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PMID:Does nitric oxide act as a cellular messenger in muscarinic endometrial secretion in the guinea-pig? 1194 18

To determine the role of the metabolites of L-arginine in its actions on picrotoxin-induced convulsions in rats, the concentrations of nitric oxide (NO) and L-citrulline were measured in the brain 30 and 60 min after the administration of L-arginine (1000 and 2000 mg/kg) or of N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg), an inhibitor of NO synthase. Animals treated similarly were challenged 30 and 60 min later with picrotoxin (5mg/kg), and the time of onset of myoclonus and clonic convulsions and the frequency of convulsions were determined. These parameters were also determined 30 and 60 min after administering L-arginine in L-NAME-pretreated (30 min) animals. Thirty minutes after the administration of L-arginine, the concentrations of both NO and L-citrulline were raised, the onset of myoclonus and clonic convulsions was delayed, and the frequency of convulsions was decreased, indicating the anticonvulsant property of L-arginine. A 60-min treatment of L-arginine produced a further increase in the concentration of L-citrulline but not that of NO and promoted the frequency of picrotoxin-induced convulsions. Pretreatment with L-NAME prevented L-arginine from raising the concentrations of both NO and L-citrulline; it also promoted the anticonvulsant actions and prevented the proconvulsant actions of L-arginine. These results lead to the conclusion that NO has no involvement in the time-dependent anti and proconvulsant actions of L-arginine on the picrotoxin convulsion model, and that L-citrulline seems to have a role in the proconvulsant action of L-arginine.
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PMID:Evidence for the involvement of L-citrulline but not nitric oxide in the proconvulsant action of the precursor L-arginine on picrotoxin-induced convulsions in rats. 1209 79

Ultrasound accelerates enzymatic fibrinolysis in vitro and in animal models and may be used as an adjunct to thrombolytic therapy. Ultrasound can also affect vascular tone directly, and we have now investigated the effect of ultrasound on tissue perfusion in a rabbit model of acute muscle ischemia to characterize the magnitude and temporal course of vasodilation and determine its mechanism. After ligation of the femoral artery of rabbits, tissue perfusion in the gracilis muscle as determined using a laser Doppler probe declined by 53% from 13.7 +/- 0.3 U to 6.4 +/- 0.2 U. The tissue became acidotic as pH declined from normal to 7.05 +/- 0.2. Application of 40 kHz ultrasound at intensities from 0.25 to 0.75 W/cm(2) progressively improved perfusion over 60 min and reversed acidosis, but these effects were both completely blocked by pre-treatment with the nitric oxide synthase inhibitor L-NAME. Nitric oxide synthase activity in muscle was measured using an assay based on the conversion of radiolabeled L-arginine to L-citrulline and demonstrated an increase of 3.6-fold following ultrasound exposure. This effect was greatest at locations close to the transducer and declined progressively away from it. Histologic examination showed greater capillary circumference in ultrasound exposed muscle compared to unexposed tissue with no other histologic changes. We conclude that the application of 40 kHz at low intensity improves perfusion and reverses acidosis in acutely ischemic muscle through a nitric oxide dependent mechanism.
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PMID:Ultrasound improves tissue perfusion in ischemic tissue through a nitric oxide dependent mechanism. 1242 7

The aim of this study was to investigate in rat gastric fundus whether L-citrulline, the co-product in the nitric oxide (NO) biosynthesis catalyzed by neuronal nitric oxide synthase (nNOS), can be converted back to the nNOS substrate L-arginine. Immunohistochemistry showed that argininosuccinate synthetase and argininosuccinate lyase, that mediate transformation of L-citrulline to L-arginine in the ureum cycle in hepatocytes, co-localize with nNOS. In longitudinal smooth muscle strips, L-arginine as well as L-citrulline (10(-3) M) was capable of completely respectively partially preventing the N(G)-nitro-L-arginine methyl ester (L-NAME) (3 x 10(-5) M)-induced inhibition of electrically induced nitrergic relaxations, whereas D-citrulline (10(-3) M) was not. The L-citrulline-mediated prevention of the L-NAME-induced inhibition was reduced by L-glutamine (3 x 10(-3) M), the putative L-citrulline uptake inhibitor, and by succinate, an argininosuccinate lyase inhibitor. The results demonstrate that the L-citrulline recycling mechanism is active in rat gastric fundus. Recycling of L-citrulline might play a role in providing sufficient amounts of nNOS substrate during long-lasting relaxations in gastric fundus after food intake.
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PMID:L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus. 1244 81

Nitric oxide (NO) plays a major role in gut mucosal protection and motility. Having demonstrated the protective effects of intravenous L-arginine (L-arg) and the NO donor, sodium nitroprusside (SNP), in an in-vivo premature piglet intraluminal model of necrotizing enterocolitis (NEC) that incorporates both mucosal damage and intestinal dysmotility, we measured the effects on NO synthase (NOS) isoenzyme activities during i.v. manipulation of the nitrergic system in the NEC-injured gut. In newborn premature Yorkshire piglets, NEC was induced in four groups by intraluminal injection of acidified casein solution in closed test loops of bowel separated by normal saline-injected control loops. Group 1 (n = 4) underwent no further treatment. Group 2 (n = 4) received concomitant continuous i.v. L-arg, a NO substrate. Group 3 (n = 6) received concomitant continuous i.v. SNP, a NO donor. Group 4 (n = 5) received concomitant continuous i.v. N-omega-nitro-L-arginine-methyl-ester (L-NAME), a non-selective NO inhibitor. Control and test gut specimens were harvested after 3 h. NO synthase activity in frozen gut segments was assessed using the (14)C-L-arg to (14)C-L-citrulline conversion assay. Total NOS (TNOS), constitutive NOS (cNOS), and inducible NOS (iNOS) activities were compared. The mean and standard error were calculated for each specimen. Group means were used to compare test and control gut enzyme activities in the different treatment groups. One-way analysis of variance and the Bonferroni post test were used to compare differences among groups. A P value of less than 0.05 was considered significant. In the L-NAME group, cNOS activity was lower than in the untreated NEC group. The SNP group had higher iNOS and TNOS activities than the L-arg group; cNOS was also higher in test and control loops in the SNP versus both L-arg and L-NAME groups. However, in L-arg control loops, cNOS activity was greater than in the L-NAME group. SNP and L-arg treatment of NEC did not significantly modify NOS isoenzyme activities. Thus, in this premature piglet 3-h model of NEC, i.v. L-NAME significantly decreases cNOS activity and correlates with our previously published histopathologic findings confirming the protective role of cNOS-derived NO in NEC-injured gut mucosa. In order to further elucidate the mechanisms involved in the mucosal protection afforded by i.v. L-arg and SNP in this NEC model, studies of a longer duration have been undertaken.
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PMID:Nitric oxide synthase isoenzyme activities in a premature piglet model of necrotizing enterocolitis: effects of nitrergic manipulation. 1247 79

1 The role of nitric oxide (NO) in the effects of low endotoxemia on gastric damage and blood flow has been evaluated in indomethacin-treated rats. 2 Pretreatment (-1 h) with endotoxin (40 micro g kg(-1)) reduced gastric damage induced by indomethacin (20 mg kg(-1)) in conscious rats. 3 Endotoxin prevented the reduction in gastric blood flow (laser Doppler flowmetry) induced by indomethacin in pentobarbital-anaesthetised rats. 4 Pretreatment with an NO-synthase (NOS) inhibitor (L-NAME, 1 mg kg(-1)) reversed the protective effect of endotoxin on gastric blood perfusion. 5 Endotoxin did not modify the expression of mRNA for endothelial NOS or inducible NOS in the gastric corpus when evaluated 1 h postinjection. However, a 3.8-fold increase in inducible NOS mRNA and a 61% reduction in endothelial NOS mRNA were observed in the gastric corpus 4 h after endotoxin administration. 6 Evaluation of both total and Ca(2+)-dependent NOS activity by analysing the rate of conversion of L-arginine to L-citrulline in gastric corpus homogenates showed no differences between animals treated with endotoxin and those treated with saline 1 or 4 h beforehand. Ca(2+)-independent NOS activity was almost non-apparent in control as well as in endotoxin-treated rats at all the time points analysed. 7 Low endotoxemia preserves blood perfusion and protects the gastric mucosa against the deleterious effects of indomethacin through the endogenous NO release. NO synthesis in response to endotoxin does not involve the inducible NOS, but probably depends on the post-translational/biochemical regulation in vivo of a Ca(2+)-dependent NOS, most probably endothelial NOS.
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PMID:Low endotoxemia prevents the reduction of gastric blood flow induced by NSAIDs: role of nitric oxide. 1277 Sep 31

Uterine cervical secretory cells receive a sympathetic cholinergic secretomotor innervation. It has been suggested that glandular nitric oxide (NO) production is a prerequisite for muscarinic-induced carbohydrate secretion in the endometrium and the seminal vesicle. A similar pattern for nerve-induced carbohydrate secretion in the cervix could be assumed. Nitric oxide synthase (NOS) activity was evaluated via formation of L-citrulline from L-arginine. The NADPH-diaphorase nitroblue technique was used for histochemical investigation. The cervix with the adjacent hypogastric nerve was placed in an isolated organ bath and the secretion was evaluated as an amount of carbohydrate. A calcium-dependent formation of citrulline was found in the cervix indicating NO formation. Strong NADPH-staining cells were found in the glandular ducts and in the glandular linings of the cervix. Stimulation of the hypogastric nerve induced carbohydrate secretion, which was inhibited by N-nitro-L-arginine methyl ester (L-NAME). D-NAME did not affect the secretory response. Carbachol and the NO donor glyceryl trinitrate (GTN) induced carbohydrate secretion in the cervical glands. No synergistic effect was noted probably due to an all-or-none type of secretion. N-nitro-L-arginine (L-NNA) and L-NAME inhibited carbachol-induced secretion. The results suggest that glandular NO production is a prerequisite for the autonomic nervous modulation of cervical secretion in the guinea-pig. This could have implications regarding fertility and fecundity.
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PMID:Nitric oxide as putative second messenger in nerve-induced cervical gland secretion in the guinea-pig. 1548 16

The free radical nitric oxide (NO), generated through the oxidation of L-arginine to L-citrulline by NO synthases (NOSs), has been shown to inhibit steroidogenic pathways. NOS isoforms are known to be present in rat and human testes. Our study examined the sensitivity of Leydig cells to NO and determined whether NOS activity resides in Leydig cells or in another cell type such as the testicular macrophage. The results showed a low level of L-[14C]arginine conversion in purified rat Leydig cell homogenates. Administration of the NOS inhibitor L-N(G)-nitro-arginine methyl ester (L-NAME), or the calcium chelator ethylenebis (oxyethylenenitrilo)tetraacetic acid (EGTA), had no effect on L-[14C]citrulline accumulation. Increased intracellular Ca2+ concentrations that were induced by a calcium ionophore, or the addition of luteinizing hormone (LH), failed to affect NO formation in intact cells that were cultured in vitro. Introduction of a high concentration of the NO precursor L-arginine did not decrease testosterone (T) production, and NOS inhibitors did not increase T biosynthesis. However, exposing Leydig cells to low concentrations of the NO donor S-nitrosoglutathione (GSNO) induced a dramatic blockade of T production under basal and LH-stimulated conditions. DNA array assays showed a low level of expression of endothelial NOS (eNOS), while the neuronal and inducible isoforms of NOS (nNOS and iNOS) were below detection levels. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses confirmed these findings and demonstrated the presence of high iNOS messenger RNA (mRNA) levels in activated testicular macrophages that produced large amounts of NO. These data suggest that, while T production in rat Leydig cells is highly sensitive to NO and an endogenous NO-generating system is not present in these cells, NOS activity is more likely to reside in activated testicular macrophages.
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PMID:Paracrine modulation of androgen synthesis in rat leydig cells by nitric oxide. 1586 5

Oxidized-1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (Ox-PAPC), found in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to synthesize chemotactic factors, such as interleukin (IL)-8. Previously, we demonstrated that the sustained induction of IL-8 transcription by Ox-PAPC was mediated through the activation of sterol regulatory element-binding protein (SREBP). We now present evidence for the role of endothelial nitric oxide synthase (eNOS) in the activation of SREBP by Ox-PAPC. Ox-PAPC treatment of EC induced a dose- and time-dependent activation of eNOS, as measured by phosphorylation of serine 1177, dephosphorylation of threonine 495, and the conversion of L-arginine to L-citrulline. Activation of eNOS by Ox-PAPC was regulated through a phosphatidylinositol-3-kinase/Akt-mediated mechanism. These studies also demonstrated that pretreatment of EC with NOS inhibitor, Nomega-nitro-L-arginine-methyl ester (L-NAME), significantly inhibited Ox-PAPC-induced IL-8 synthesis. Because SREBP activation had been previously shown to regulate IL-8 transcription by Ox-PAPC, we examined the effects of L-NAME on Ox-PAPC-induced SREBP activation. Our data demonstrated that Ox-PAPC-induced SREBP activation and expression of SREBP target genes were significantly reduced by pretreatment with L-NAME. Interestingly, treatment of EC with NO donor, S-nitroso-N-acetylpenicillamine, did not activate SREBP, suggesting that NO alone was not sufficient for SREBP activation. Rather, our findings indicated that superoxide (O2*-), in combination with NO, regulated SREBP activation by Ox-PAPC. We found that Ox-PAPC treatment generated O2*- through an eNOS-mediated mechanism and that mercaptoethylguanidine, a peroxynitrite scavenger, reduced SREBP activation by Ox-PAPC. Taken together, these findings propose a novel role for eNOS in the activation of SREBP and SREBP-mediated inflammatory processes.
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PMID:Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids. 1657 11

1. We further characterized the effect of endothelins (ETs) on receptor-mediated phosphoinositide (PI) turnover, nitric oxide synthase (NOS) activation, and cGMP formation in whole rat adrenal medulla. 2. The PI hydrolysis was assessed as accumulation of inositol monophosphates (InsP(1)) in the presence of 10 mM LiCl in whole tissue and the analysis of inositol-1-phosphate by Dowex anion exchange chromatography. NOS activity was assayed by monitoring the conversion of radiolabeled L-arginine to L-citrulline. Cyclic GMP formation was assessed as accumulation of cGMP in whole tissue in the presence of phosphodiesterase inhibition, and the amount of cGMP formed was determined by radioimmuno-antibody procedure. 3. ET-1 and ET-3 increased PI turnover by 30% in whole adrenal medulla prelabeled with [(3)H] myoinositol. Both ETs isoforms, at equimolar doses, increased NOS activity and cGMP levels in similar degree. The selective ET(B) receptor agonist, IRL-1620, also increased cGMP formation, mimicking the effects of ETs, while IRL-1620 did not alter the PI metabolism. ETs-induced InsP(1) accumulation and cGMP was dependent on extracellular calcium. The effect of ETs on PI turnover was inhibited by neomycin. The L-arginine analogue, N-nitro-L-arginine (L-NAME), and two inhibitors of soluble guanylyl cyclase, methylene blue and ODQ, significantly inhibited the increase in cGMP production induced by ETs or IRL-1620. The selective ET(A) receptor antagonist, BQ 123, inhibited the ETs-induced increase in PI turnover, while the selective ET(B) receptor antagonist, BQ 788, was ineffective. Likewise, BQ 788, significantly inhibited ET-1- or ET-3-induced NOS activation and cGMP generation but not ETs-induced InsP(1) accumulation. 4. Our data indicate that stimulation of PI turnover and NO-induced cGMP generation constitutes ETs signaling pathways in rat adrenal medulla. The former action is mediated through activation of ET(A) receptor, while the latter through the activation of ET(B) receptor. These results support the role of endothelins in the regulation of adrenal medulla function.
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PMID:Endothelin signaling pathways in rat adrenal medulla. 1689 61


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