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)

Intracellular recordings were made from neurones E-8, E-16 and E-13a in the visceral ganglion of Helix aspersa. GSPYFVamide inhibits the activity of these neurones and the role of a second messenger system in this inhibition was investigated. 8-Bromo-cGMP, 100 microM was found to potentiate this inhibition while ODQ, 100 microM, an inhibitor of guanylyl cyclase, almost completely blocked GSPYFVamide-induced inhibition. Four NO donors sodium nitroprusside, 100 microM, sodium nitrite, 1 mM, SNOG, 50 microM, and SNAP, 10-50 microM, all potentiated the GSPYFVamide-induced inhibition. L-NAME, 100-1000 microM, a competitive inhibitor of NOS, blocked the GSPYFVamide-induced inhibition. In some cases recovery was only partial. The possible role of NO in modulating the inhibitory response to GSPYFVamide is discussed.
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PMID:Evidence for the involvement of nitric oxide in the inhibitory effect of GSPYFVamide on Helix aspersa central neurones. 971 72

Excessive nitric oxide (NO) synthesis, by inducible NO synthase (iNOS), has been implicated in the pathogenesis of inflammatory diseases such as rheumatoid arthritis. We investigated the pathophysiological role of NO using an adjuvant-induced arthritis model. Kinetics of iNOS mRNA expression in paw and spleen showed that it was induced from an early stage of the disease. To further characterize the pathophysiological relevance of iNOS induction in spleen, the mitogenic response of spleen cells was examined. ConA-induced proliferation of spleen cells from arthritic rats was completely suppressed in comparison to normal rats. Elevation of nitrite, which could be converted from NO, was also observed in the culture supernatants. Addition of three NOS inhibitors, S-(2-aminoethyl) isothiouronium bromide (ITU), aminoguanidine (AG) and LNG-nitroarginine methyl ester (L-NAME) all reduced the nitrite level and restored the proliferative response dose-dependently. These NOS inhibitors also showed anti-arthritic effects. Daily subcutaneous administration of either ITU at 50 mg/kg or AG at 200 mg/kg suppressed the paw swelling by 50% in arthritic rats on day 18. Oral administration of L-NAME at 30 mg/kg showed a tendency to suppress the development of arthritis from day 11 to day 15. However, drug-induced hypertension was observed with L-NAME due to poor selectivity for iNOS isozyme. These results suggest that augmented NO synthesis, via iNOS induction, may be partly involved in the pathogenesis of adjuvant-induced arthritis by causing defects in lymphocyte function. Thus, selective inhibition of iNOS might be beneficial for the treatment of immunological abnormalities associated with inflammatory diseases.
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PMID:Immunological abnormality associated with the augmented nitric oxide synthesis in adjuvant-induced arthritis. 971 83

To determine whether the venous circuit constitutively produces nitric oxide (NO), we infused the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) into anesthetized and mechanically ventilated pigs and measured venous circuit parameters. We measured cardiac output (Q) by thermodilution and obtained arterial (Part), central venous pressure (in the inferior vena cava), right atrial (Pra), pulmonary artery (PAP), and pulmonary capillary wedge pressures. A balloon was transiently inflated in the right atrium to stop venous return and obtain mean circulatory filling pressure (MCFP). Venous compliance (Cv) was measured by volume boluses. Starling curves were obtained from changes in Q with changes in Pra from the boluses. Resistance to venous return (RVR) was calculated from (MCFP - Pra)/Q. After baseline measurements, we infused 25 mg/kg of L-NAME over 10 min in seven pigs and monitored them for a further 2 h. Three others served as time controls and showed no significant hemodynamic changes. L-NAME markedly decreased cardiac output from 3.8+/-0.86 to a low of 2.0+/-0.2 L/min, and increased blood pressure from 114+/-16 to 144+/-11 mm Hg and pulmonary artery pressure from 15+/-2 to 30+/-12 mm Hg (p < 0.05). MCFP increased from 9.1+/-1.2 to 11.4+/-2.4 mm Hg (p < 0.05); Cv did not change. Cardiac function curves were markedly depressed and flattened and remained depressed for 2 h. The increase in RVR of 167% from 1.8+/-0.6 mm Hg/L/min at baseline to 5.4+/-3.7 mm Hg/L/min (p < 0.05) was similar to the 188% increase in systemic vascular resistance. These data indicate that constitutive release of NO decreases baseline venous resistance and increases capacitance. There also appears to be a worsening of cardiac function when NOS is inhibited.
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PMID:Evidence for constitutive release of nitric oxide in the venous circuit of pigs. 973 48

The enzyme heme oxygenase, which exists in inducible (HO-1) and constitutive (HO-2) isoforms, catalyzes the degradation of heme to biliverdin and CO in mammalian tissues. CO has been implicated in the control of vascular tone in a manner similar to that for NO. In the present study, we investigated the contribution of the heme oxygenase/CO pathway to the modulation of acute hypertensive responses in vivo induced by (1) alphaalphaHb, a chemically modified hemoglobin known to scavenge NO, and (2) NG-nitro-L-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Experiments were carried out in conscious rats in which femoral arteries and veins were surgically catheterized 1 or 5 days before treatment with the vasoconstrictor agents. Intravenous infusion of alphaalphaHb (8% solution) or L-NAME (30 micromol/kg) [corrected] produced an acute and significant increase in mean arterial pressure (P<0.05) in rats at 5 days after catheter implantation. In contrast, no change in blood pressure was observed when alphaalphaHb or L-NAME was infused 1 day after the surgical intervention. The suppression of the hypertensive response observed at 1 day after surgery correlated with a significant (P<0.05) HO-1 expression in aorta, heart, and liver as well as increased aortic CO production and cGMP levels. At 1 day after surgery, pretreatment of animals with the heme oxygenase inhibitor zinc protoporphyrin IX (50 micromol/kg IP) markedly decreased aortic CO and cGMP levels and completely restored the vasoconstrictor effects of both alphaalphaHb and L-NAME. These results provide evidence for a crucial role of the heme oxygenase/CO pathway in the regulation of blood pressure under stress conditions in vivo.
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PMID:Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. 973 80

Chronic blockade of NO production induces hypertension and early occlusive and fibrotic end-stage organ damage owing to vascular lesions in the brain, kidney, and heart. In this study, we evaluated the inflammatory phenotypic changes induced in the arterial wall by chronic N(G)-nitro-L-arginine methyl ester (L-NAME) administration and the effect of an angiotensin II receptor (AT1) antagonist, irbesartan, on these changes. For this purpose, 2 groups of rats received L-NAME in the drinking water (50 mg x kg(-1) x d(-1)) for 2 months. One group received no other treatment and the other was treated with irbesartan (10 mg x kg(-1) x d(-1)). A third group (controls) received neither L-NAME nor irbesartan. After 8 weeks, plasma, aortas, and left ventricles were sampled from all 3 groups. Expression of inducible NO synthase (iNOS) was evaluated at both the mRNA (quantitative reverse transcription-polymerase chain reaction) and the protein (Western blot and immunohistochemistry) level in the aorta. Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was evaluated by reverse transcription-polymerase chain reaction, Western immunoblotting, and immunohistochemistry; inflammatory cell infiltration by immunohistochemistry; and fibrosis by Sirius red staining. Chronic L-NAME administration induced the expression of iNOS in the aorta, which was localized in smooth muscle cells as shown by immunohistochemistry and NADPH diaphorase activity. ICAM-1 and VCAM-1 expression was also increased in aortas of L-NAME-treated rats. These phenotypic changes of the vascular wall were associated with inflammatory cell infiltration and fibrosis in the heart. All of these pathological phenomena were prevented by the angiotensin II antagonist irbesartan. The proinflammatory phenotypic changes of the vascular wall induced by blockade of NOS activity could be involved in the interaction between endothelial dysfunction and the development of arteriosclerosis.
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PMID:Chronic blockade of NO synthase activity induces a proinflammatory phenotype in the arterial wall: prevention by angiotensin II antagonism. 974 29

After removing nonspecific immunoreactivities from crude extract by immunoaffinity chromatography, an immunoreactive-band at 60 kDa of constitutive nitric oxide synthase (cNOS) from Saccharomyces cerevisiae was detected by Western blot using mouse monoclonal anti-neuronal NOS (cNOS). The activity of yeast cNOS, which was prepared by either histone-agarose chromatography or anti-neuronal NOS immunoprecipitation, was monitored by the formation of citrulline. Yeast cNOS was activated in the presence of calmodulin and arginine, whereas it was inhibited by L-NAME, a mammalian NOS inhibitor. Moreover, actinomycin-D decreased the extracellular and the intracellular levels of nitrate and nitrite which had been converted from NO. The results suggest that cNOS occurs in unicellular eukaryotes and the enzyme activity can be regulated.
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PMID:Constitutive nitric oxide synthase in Saccharomyces cerevisiae. 976 6

In this paper, we evaluated the hypothesis that prostaglandin F2 alpha (PGF2 alpha) regulates NOS activity and we also investigated, by means of nitric oxide inhibitors (N-monomethyl-L-arginine monoacetate, L-NMMA) the role of endogenous NO on PGF2 alpha-induced contractions in rat oviduct. NOS activity was determined by measuring the conversion of 14[C]-L-arginine to 14[C]-L-citrulline on oviductal homogenates from estrogenized rats (1 microgram/rat). The presence of PGF2 alpha (10(-8) M) in the incubation medium produced an increase in NOS activity (p < or = 0.05). The effect of the prostanoid was blocked completely by the presence of two NOS inhibitors: N-nitro-L-arginine methyl ester (L-NAME, 0.6 mM) and aminoguanidine (Ag, 0.5 mM). These results suggested that PGF2 alpha could be modulating the Ca(2+)-independent NOS activity. We determined NOS activity using 1 mM EGTA, a chelator of Ca2+, in a free Ca2+ medium. These results indicated that PGF2 alpha produces an increase in Ca(2+)-independent NOS activity (p < or = 0.05). PGF2 alpha induces contraction of the oviductal smooth muscle in a concentration dependent manner. L-NMMA enhanced PGF2 alpha induced contraction of the oviduct, providing indirect evidence that there is a basal release of NO in the oviduct, which may reduce and/or modulate the contractile effects of PGF2 alpha.
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PMID:Effect of prostaglandin F2 alpha (PGF2 alpha) on oviductal nitric oxide synthase (NOS) activity: possible role of endogenous NO on PGF2 alpha-induced contractions in rat oviduct. 978 85

The role of neural nitric oxide synthase (nNOS) in regulating blood pressure (BP) remains uncertain. Recently it was reported that in mice lacking functional endothelial NOS (eNOS) genes (-/-), acute administration of a nonselective NOS inhibitor, Nw-nitro-L-arginine, decreased mean BP, suggesting that NO released by non-eNOS isoforms increases BP. Because the inducible NOS isoform is not constitutively expressed and when induced causes hypotension, we hypothesize that it is NO produced by nNOS that increases BP in the absence of eNOS activity. To test this hypothesis, we studied the acute effect of selective and nonselective nNOS inhibitors on BP and cerebellar NOS activity in eNOS (-/-), wild-type (+/+), and heterozygous (+/-) mice as well as in +/+ mice with renovascular hypertension. Because it is not known whether the decrease in BP caused by acute NOS inhibition in -/- mice can occur chronically, we also studied the effect of chronic NOS inhibition on both BP and cerebellar NOS activity. eNOS (-/-) mice had higher BP than +/+ or +/-mice, and acute administration of the selective nNOS inhibitor 7-nitroindazole (7-NI) decreased their mean BP from 137+/-13 to 124+/-12 mm Hg (P<0.01). In +/+, +/-, or renovascular hypertensive +/+ mice, 7-NI caused a small but insignificant rise from 105+/-5 to 110+/-6 mm Hg, from 115+/-9 to 119+/-13 mm Hg, and from 146+/-6 to 150+/-6 mm Hg, respectively. Fifteen minutes after administration of 7-NI, cerebellar NOS activity decreased by 70%; however, this inhibitory effect was brief, since 2 hours after 7-NI administration NOS returned toward control values. Chronic oral or intraperitoneal administration of 7-NI did not inhibit cerebellar NOS activity, whereas the nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) decreased this activity by 50%. Therefore, we studied the effect of chronic L-NAME administration (4 weeks) on BP. In -/- mice, chronic L-NAME administration decreased BP from 135+/-4 to 120+/-3 mm Hg (P<0.05), whereas in +/+ and +/-mice, as expected, it increased BP from 109+/-2 to 125+/-3 mm Hg (P<0.001) and from 107+/-6 to 119+/-5 mm Hg (P<0.02), respectively. After L-NAME administration was stopped, BP returned to baseline. These results suggest that in eNOS -/- mice, NO derived from nNOS increases BP both acutely and chronically.
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PMID:Role of nNOS in blood pressure regulation in eNOS null mutant mice. 982 44

Considerable evidence has linked hydroxyl radicals (.OH) to excitotoxicity. Glutamate infused through a microdialysis probe into rat striatum induced a massive .OH production, which was completely blocked by PBN and attenuated by dizocilpine, 2-amino-5-phosphonopentanoic acid (AP-5), NG-nitro-L-arginine methyl ester (L-NAME) and mepacrine. Thus, we suggest that the neurotoxic effects of glutamate in vivo may derive from an increased formation of .OH resulting from excessive activation of NMDA receptors and downstream enzymes such as NOS and PLA2.
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PMID:A microdialysis study investigating the mechanisms of hydroxyl radical formation in rat striatum exposed to glutamate. 985 22

A close association of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) neurons with the retinal vasculature has been reported and it is proposed that activation of these neurons could be the mechanism by which retinal blood flow and metabolism are linked. Further, advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic retina and aminoguanidine (AG), an inhibitor of advanced glycation, has been shown to attenuate the development of AGE accumulation as well as the progression of experimental diabetic retinopathy. This study examined the effects of short (1 and 3 weeks) and long term (32 weeks) diabetes on nNOS-containing neurons of the retina using NADPH diaphorase (NADPHd) histochemistry. In addition, the effect of aminoguanidine (an inhibitor of advanced glycation and NOS) and NG-nitro-L-arginine methyl ester (L-NAME) (a non-selective NOS inhibitor) on retinal nNOS-containing neurons was examined in short and long term control and diabetic rats. In a separate study, the effect of 2,3 diamino-phenazine (NN0028) (an inhibitor of advanced glycation, but not NOS) was examined in short term (3 weeks) diabetic rats. The number of NADPHd-positive neurons per retina was reduced after one week of diabetes and remained decreased in long term diabetic rats, an effect not observed in diabetic rats rendered euglycaemic by intensified insulin treatment. Treatment of diabetic animals with aminoguanidine or NN0028 prevented the depletion in the nNOS-containing neuron number, an effect not reproduced by L-NAME. These studies suggest that the action of AG in restoring the number of nNOS-containing retinal neurons is mediated by the inhibition of AGE formation. The depletion of nNOS-containing neurons may contribute to alterations in the autoregulation of blood flow which occurs in diabetes.
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PMID:Depletion of nitric oxide synthase-containing neurons in the diabetic retina: reversal by aminoguanidine. 986 8


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