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. 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

The goal of this study was to determine the arterial pressure and renal excretory responses to a continuous intravenous infusion of 7.4 nmol/kg per minute of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in conscious rats. Studies were conducted in six groups of Sprague-Dawley rats with indwelling arterial and venous catheters over periods lasting 12 to 26 days. In the first group of rats, L-NAME infusion for 9 days caused a sustained increase in arterial pressure, and on the ninth day arterial pressure was increased 29 mm Hg. Infusion of L-NAME at the higher dose of 37 nmol/kg per minute for 9 days caused no greater increase in arterial pressure than the lower dose. Sodium and volume balances and phenylephrine pressor sensitivity were unchanged during L-NAME administration at 7.4 nmol/kg per minute; plasma renin activity increased 2.5-fold, but the vasodepressor and vasodilator responses to acetylcholine and bradykinin were unchanged. Arterial pressure remained significantly increased 7 days after L-NAME was stopped, but in another group of rats, intravenous L-arginine infusion caused arterial pressure to return to control within 1 day. This same dose of L-arginine was administered for 7 days intravenously, and neither arterial pressure nor sodium balance changed. In other groups of rats, L-arginine was administered in conjunction with L-NAME; this prevented any change in arterial pressure, whereas D-arginine did not. In conclusion, the data suggest that continuous intravenous infusion of L-NAME causes sustained increases in arterial pressure in conscious rats without any sodium or water retention. The hypertension is accompanied by increases in plasma renin activity and can be prevented with intravenous L-arginine administration.
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PMID:Long-term cardiovascular role of nitric oxide in conscious rats. 830 27

1. The role played by the endothelium-derived relaxing factor (EDRF), nitric oxide (NO) in the regulation of blood flow to the skeletal muscle vasculature of the dog skinned hindlimb has been determined by examining the effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) upon (i) basal iliac artery blood flow, (ii) vasodilator responses to endothelium-dependent and -independent agonists and (iii) reactive hyperaemic responses to arterial occlusion. 2. L-NAME (0.1-3 mg min-1) infused directly into the iliac artery dose-dependently reduced basal iliac artery blood flow by a maximum of 48.6 +/- 6.9% (n = 4) and also increased mean systemic arterial blood pressure by 25.6 +/- 5.0 mmHg (n = 4) (at 3 mg min-1 L-NAME). 3. Over the same dose range, L-NAME also inhibited the peak vasodilator responses to intra-arterially administered, submaximal bolus doses of the endothelium-dependent agonists, bradykinin (3-300 ng) and acetylcholine (30-300 ng) by approximately 40%. In contrast, peak vasodilator responses to the endothelium-independent agonists, sodium azide (3-30 micrograms) and adenosine (0.3-1 mg), and peak reactive hyperaemic responses to arterial occlusion (60 s) were largely unaffected by L-NAME. 4. The dose-related effects of L-NAME on basal iliac artery blood flow, mean systemic arterial blood pressure and endothelium-dependent vasodilator responses were significantly attenuated by pretreatment with L-arginine (100 mg min-1) followed by co-infusion of L-arginine (100 mg min-1) with L-NAME. 5. In conclusion, these data suggest that NO plays some role in regulating basal blood flow and in mediating the vasodilator responses to the endothelium-dependent agonists bradykinin and acetylcholine in the skeletal muscle vasculature of the dog hindlimb. The substantial component (~60%) of the peak vasodilator responses to bradykinin and acetylcholine, unaffected by L-NAME, may be independent of NO, or be mediated by an alternative EDRF-dependent but L-NAME-insensitive mechanism.
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PMID:The effect of NG-nitro-L-arginine methyl ester upon basal blood flow and endothelium-dependent vasodilatation in the dog hindlimb. 846 62

We have investigated the effects of a nitric oxide (NO) biosynthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the bombesin-evoked contraction of guinea pig parenchymal lung strips. The bombesin-induced contractions of lung strips were significantly increased after L-NAME (300 micro)) pre-treatment. The maximal response was increased (P < 0.01) by 37% after L-NAME treatment when compared with the control group. The pD2 value was not influenced by L-NAME pre-treatment. The enhancement of the bombesin-induced contraction caused by L-NAME was reversed by addition of an excess of the NO precursor L-arginine (600 microM) but not by the addition of its inactive enantiomer D-arginine (600 microM). Like L-NAME, methylene blue (1 microM), an agent that inhibits the soluble guanylyl cyclase activated by NO, significantly increased (P < 0.01) the maximal contraction induced by bombesin (183 +/- 16 mg) when compared with the control group (141 +/- 15 mg). When tested against other agonist-induced contractions, L-NAME did not change the responsiveness of parenchymal lung strips to bradykinin or carbachol but significantly increased lung contraction induced by histamine. NO synthesis inhibition resulted in a pronounced increase in the bombesin-induced contraction of guinea-pig lung strips. Our results suggest that bombesin contributes to NO synthesis and release which then acts to reduce the contraction of the lungstrip in response to bombesin.
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PMID:Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide. 853 70

Biochemical signaling determines the specific action of vasomediators in the control of microvascular permeability and tone. We tested the hypothesis that nitric oxide (NO) synthesis is involved in the biochemical signaling pathway of platelet activating factor (PAF). The cheek pouch of anesthetized male Syrian hamsters was used as a microvascular model. Vessel diameter [expressed as the ratio of the experimental to the control (e/c) diameter, with control diameter normalized to 1] and extravasation of FITC-dextran 150 by integrated optical intensity (IOI) were determined using intravital fluorescent microscopy and computer-assisted digital image analysis. N-Nitro-L-arginine methyl ester (L-NAME) at 10(-5) and 10(-6) M and N-nitro-L-mono-methyl arginine (L-NMMA) at 10(-4) and 10(-5) M were used as inhibitors of NO synthase (NOS). Acetylcholine (ACh) and bradykinin were used as indirect indices of NOS activation. L-NAME and L-NMMA attenuated both ACh and bradykinin vasodilatory effects as well as the bradykinin-induced increase in vascular permeability. Topical PAF (10(-7) M) caused vasoconstriction (mean +/- SEM e/c ratio = 0.3 +/- 0.1) and increased IOI from a normalized baseline of 0 to 67.4 +/- 12.8. Topical administration of L-NAME produced differential effects on the series-arranged arterioles but had no effect on postcapillary venular permeability. L-NMMA did not influence the basal arteriolar diameter, but at 10(-5) M it caused a small increase in permeability (IOI = 14.3 +/- 4.2). In the presence of NOS inhibitors, PAF caused a reduced arteriolar constriction (e/c ratio = 0.6 +/- 0.1) relative to PAF alone. Both NOS inhibitors reduced the PAF-stimulated increase in vasopermeability. At 10(-5) M L-NMMA, the PAF-stimulated IOI mean value was 26.1 +/- 5.2, while at 10(-4) M L-NMMA the PAF-stimulated IOI was 15.2 +/- 2.6 compared to 10(-7) M PAF (67.4 +/- 12.8). These results support our hypothesis that NO synthesis is a step in the biochemical signaling pathway of the postcapillary cellular responses to PAF.
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PMID:Platelet activating factor modulates microvascular permeability through nitric oxide synthesis. 853 2

1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the impaired endothelial function in hypertension, but the mediators underlying the promoted endothelium-dependent dilatation have not been fully characterized. Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium-dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and quinapril-treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the relaxations in both WKY groups and quinapril-treated SHR, and completely inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was prevented by precontraction of the preparations with potassium chloride (KCl), no differences were found in relaxations to ACh and ADP between the study groups. In addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant relaxations to ACh were partially prevented by apamin, an inhibitor of calcium-activated potassium channels. 3. Interestingly, in quinapril-treated SHR but not in the other groups, exogenous bradykinin potentiated the relaxations to ACh in both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of endothelium-intact rings to NA was reduced in SHR by quinapril, and was more effectively increased by L-NAME in quinapril-treated than untreated SHR. 5. In conclusion, since the relaxations to ACh and ADP in quinapril-treated SHR were augmented in the absence and presence of NO synthesis inhibition but not under conditions which prevented hyperpolarization, enhanced endothelium-dependent relaxation after long-term ACE inhibition can be attributed to increased endothelium-dependent hyperpolarization. However, the potentiation of the response to ACh by exogenous bradykinin in quinapril-treated SHR, as well as the increased attenuating effect of the endothelium on NA-induced contractions in these animals appear to result from enhanced endothelium-derived NO release.
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PMID:Endothelial function in spontaneously hypertensive rats: influence of quinapril treatment. 854 88

The nitric oxide (NO) production by porcine aortic valve endothelial cells was estimated in cusps incubated at 37 degrees C by measuring their cyclic GMP content and the nitrite levels of the incubation medium. After a stabilization period, incubation for 5 min with acetylcholine, bradykinin, ADP and bovine thrombin resulted in a receptor-mediated increase in cyclic GMP which could be blocked by EGTA, N-omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA). Incubation with lipopolysaccharide (endotoxin) from E. coli O111:B4 or bovine for 5 h, dose-dependently increased nitrite production as well as cyclic GMP content. The elevated nitrite production was completely abolished in the presence of the protein synthesis inhibitor cycloheximide, was reduced by more than 50% by dexamethasone but was not affected by EGTA. L-NMMA dose-dependently reduced the increased nitrite production and cyclic GMP content. These results suggest that besides the presence of a constitutive NO synthase in porcine aortic valve endothelial cells thrombin, like lipopolysaccharide, triggers the de novo expression of an inducible Ca(2+)-independent NO synthase.
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PMID:Thrombin triggers the de novo expression of an inducible NO synthase in porcine aortic valve endothelial cells. 856 77

Recent reports suggest that endothelial-dependent relaxant factor, recognized as nitric oxide (NO), reduces myocardial contractility. Here, we showed that both exposures to acetylcholine and bradykinin for 30 min increased cyclic guanylate monophosphate (cyclic GMP) in isolated rat cardiomyocytes. These increases in cyclic GMP were blunted by NW-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Hypoxia augmented the cyclic GMP accumulation due to exposures to acetylcholine and bradykinin, which were blunted by L-NAME. The increases in cyclic GMP due to acetylcholine and bradykinin during normoxic and hypoxic conditions were not blunted by aminoguanidine, an inhibitor of inducible NO synthase. These findings revealed that NO is produced in cardiomyocytes due to stimulation of NO synthase and modulates their own guanylate cyclase, which was augmented by hypoxia. NO production, through NO synthase in cardiomyocytes, may constitute autocrine regulations of myocardial contractility and paracrine regulations of coronary vasodilation and platelet aggregation.
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PMID:Evidence for nitric oxide generation in the cardiomyocytes: its augmentation by hypoxia. 857 31

1. Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators participate in the neurogenic vasodilatation caused by SNP. Blood flow in the plantar hindpaw skin of urethane-anaesthetized rats was measured by laser Doppler flowmetry. 2. The hyperaemic responses to intraplantar administration of the NO donors SNP (150 pmol) and 3-morpholino-sydnonimine (SIN-1, 15 nmol) were attenuated by 45% and 61%, respectively, after injection of the CGRP antagonist, CGRP8-37 (50 nmol kg-1, i.v.) which did not significantly change baseline blood flow. 3. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 15 mg kg-1, i.v.), the bradykinin antagonist Hoc-140 (100 nmol kg-1, i.v.) and the histamine antagonists, pyrilamine (2 mg kg-1, i.v.) plus cimetidine (10 mg kg-1, i.p.) were without effect on baseline blood flow and the vasodilatation caused by SNP. 4. The cyclo-oxygenase inhibitors, indomethacin (10 mg kg-1, i.p.) and flurbiprofen (5 mg kg-1, i.p.) depressed the SNP-induced hyperaemia by 65% and 42%, respectively, without altering baseline blood flow. The ability of CGRP8-37 to inhibit the vasodilator response to SNP was lost in indomethacin-treated rats. 5. Intraplantar administration of prostaglandin E2 (PGE2, 15 pmol) evoked cutaneous vasodilatation which was attenuated by 66% after administration of CGRP8-37 but remained unaltered by indomethacin or L-NAME. 6. These data indicate that the neurogenic hyperaemia which in rat skin is induced by intraplantar administration of NO donors involves the formation of prostaglandins which in turn cause release of the vasodilator peptide, CGRP, from perivascular afferent nerve fibres.
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PMID:Mediation by prostaglandins of the nitric oxide-induced neurogenic vasodilatation in rat skin. 858 Dec 70

To determine whether nitric oxide (NO) regulates mucus secretion from airway submucosal glands which are the main source of human airway secretion, we examined the effects of NO synthase inhibitors (L-NAME and L-NMMA) on mucus glycoprotein (MGP) secretion from feline and human airway explants (with epithelium) and isolated submucosal glands. MGP secretion was estimated by measuring trichloroacetic-acid (TCA) precipitable [H3]-glycoconjugates using secretory indices. NO synthase inhibitors alone did not alter significantly MGP secretion from explants or isolated glands. Pretreatment with NO synthase inhibitors significantly inhibited both methacholine (MCh) and bradykinin (BK)-induced secretion from isolated glands, but not significantly inhibit the secretion from explants. The inhibition by L-NAME was reversed by the addition of L-arginine in both MCh- and BK-induced secretions from isolated glands. Further, a NO generator isosorbide dinitrate induced a significant increase in the secretion. These findings suggest that endogenous NO has a stimulatory action in airway submucosal gland secretion and directly regulates the secretion from submucosal glands independently of superficial epithelial cells.
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PMID:Nitric oxide regulation of glycoconjugate secretion from feline and human airways in vitro. 861 Feb 12

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