Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.13.39 (NO synthase)
 15,778 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These experiments demonstrate that exposure of cultured endothelial cells (EC) to well-defined laminar fluid flow results in an elevated rate of NO production. NO production was monitored by release of NOx (NO2- + NO3(2-) and by cellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration. NO synthase (NOS) inhibitor blocked the flow-mediated stimulation of both NOx and cGMP, indicating that both measurements reflect NO production. Exposure to laminar flow increased NO release in a biphasic manner, with an initial rapid production consequent to the onset of flow followed by a less rapid, sustained production. A similar rapid increase in NO production resulted from an increase in flow above a preexisting level. The rapid initial production of NO was not dependent on shear stress within a physiological range (6-25 dyn/cm2) but may be dependent on the rate of change in shear stress. The sustained release of NO was dependent on physiological levels of shear stress. The calcium (Ca2+) or calmodulin (CaM) dependence of the initial and sustained production of NO was compared with bradykinin (BK)-mediated NO production. Both BK and the initial production were inhibited by Ca2+ and CaM antagonists. In contrast, the sustained shear stress-mediated NO production was not affected, despite the continued functional presence of the antagonists. Dexamethasone had no effect on either the initial or the sustained shear stress-mediated NO production. An inducible NOS does not, therefore, explain the apparent Ca2+/CaM independence of the sustained shear stress-mediated NO production.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. 816 25

1. The possibility of an interaction between the motor sympathetic and inhibitory non-adrenergic, non-cholinergic (NANC) nerves in the rat anococcygeus was investigated using L-NG-nitro-arginine (L-NOARG), an inhibitor of L-arginine: NO synthase. 2. L-NOARG (50 microM) increased contractions induced by field stimulation (20 s trains; 0.5-40 Hz); overall, the frequency-response curve was displaced six-fold to the left. D-NOARG (50 microM) was without effect. 3. The potentiation produced by L-NOARG was reversed by 200 microM L-, but not D-, arginine. 4. L-NOARG had no effect on contractions induced by exogenous noradrenaline (NA) or on field stimulation-induced overflow of tritium from muscles previously loaded with [3H]-NA. 5. It is concluded that the endogenous nitrate NANC transmitter does not influence release of NA from the sympathetic nerves and the potentiation of contractions induced by field stimulation in the presence of L-NOARG most probably results from removal of the opposing relaxing influence of concomitantly released NANC transmitter.
 ...
PMID:The influence of L-NG-nitro-arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle. 851 23

We investigated the cytotoxic effects of various cytokines secreted by macrophages or T lymphocytes on luteal cells, and the role of nitric oxide (NO) produced by luteal cells in cytotoxic actions of cytokines. Mouse luteal cells were cultured in serum-free medium with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta) alone, or with various combinations of these cytokines for 6 days. Cytotoxic actions of cytokines and NO production by luteal cells were evaluated by number of viable cells and the amount of nitrite and nitrate (stable metabolites of NO) in medium, respectively. IFN-gamma (1000 U/ml), TNF-alpha (3000 U/ml), or IL-1 beta (30 U/ml) alone, and the combination of TFN-alpha and IL-1 beta (10 U/ml) did not decrease number of viable cells and was without effects on NO production. The combination of IFN-gamma and IL-1 beta (10 U/ml) also did not decrease the number of viable cells, while it increased NO production a little but significantly. Combinations of INF-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and IL-1 beta (10 U/ml) markedly decreased number of viable cells. The combination of IFN-gamma and TNF-alpha increased NO production a little but significantly, and the combination of three cytokines (IFN-gamma, TNF-alpha, and IL-1 beta) caused a greater increase in NO production. An NO synthase inhibitor, L-NG-monomethy-L-arginine (0.5 mM) or aminoguanidine (0.5 mM) abolished increases in NO production induced by combinations of IFN-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and IL-1 beta completely without effects on number of viable cells. The present results indicate that combinations of cytokines including IFN-gamma and TNF-alpha induce death of cultured mouse luteal cells, and that the cytotoxic actions of these cytokines are independent of NO production by luteal cells.
 ...
PMID:Cytotoxic actions of cytokines on cultured mouse luteal cells are independent of nitric oxide. 854 Dec 25

We investigated whether gamma interferon (IFN-gamma; a Th1 cytokine), tumor necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4; a Th2 cytokine) modulate nitric oxide (NO) production in vivo during blood stage infection with Plasmodium chabaudi AS. Treatment of resistant C57BL/6 mice, which resolve infection with P. chabaudi AS and produce increased levels of IFN-gamma, TNF-alpha, and NO early during infection, with anti-IFN- gamma plus anti-TNF-alpha monoclonal antibodies (MAbs) resulted in a reduction of both splenic inducible NO synthase mRNA and serum NO3- levels by 50 and 100%, respectively. Treatment with the anti-TNF-alpha MAb alone reduced only serum NO3- levels by 35%, and treatment with the anti-IFN-gamma MAb alone had no effect on NO production by these mice during infection. Susceptible A/J mice, which succumb to infection with P. chabaudi AS and produce increased levels of IL-4 but low levels of IFN-gamma, TNF-alpha, and NO early during infection, were treated with an anti-IL-4 MAb. The latter treatment had no effect on NO production by this mouse strain during infection. In addition, our results also demonstrate that treatment of resistant C57BL/6 mice with anti-IFN-gamma plus anti-TNF-alpha MAbs affects, in addition to NO production, other traits of resistance to P. chabaudi AS malaria such as the peak level of parasitemia and the development of splenomegaly. Furthermore, the change in spleen weight was shown to be an IFN-gamma-independent effect of TNF-alpha. Treatment of susceptible A/J mice during infection with an anti IL-4 MAb had no effect on these markers of resistance. Thus, these results demonstrate that TNF-alpha and IFN-gamma are critical in the regulation of NO production and other traits of resistance during P. chabaudi AS malaria in C57BL/6 mice. These data also indicate that treatment with an anti-IL-4 antibody alone is not able to induce NO production or confer resistance to A/J mice against P. chabaudi AS malaria.
 ...
PMID:In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice. 855 72

Organic nitrates are considered nitric oxide donors in that they have been shown to form nitric oxide in vitro and in vivo. Nitroglycerin is an organic nitrate which possesses peculiar activities mediated, to some extent, by the central nervous system via the noradrenergic system. Previous reports have shown that systemic nitroglycerin is able to induce Fos expression in brain nuclei which are known to contain nitric oxide synthesizing enzyme. Neuronal NADPH-diaphorase has been shown to be a nitric oxide synthase. Thus, in this study we used NADPH-diaphorase histochemistry to evaluate the distribution of Fos-immunoreactive cells within neurons which contain nitric oxide synthase. The data showed co-localization of Fos with NADPH-diaphorase activity in numerous neurons of the paraventricular and supraoptic nuclei of the hypothalamus. In the brainstem, a few neurons were doubly labeled for Fos and NADPH-diaphorase activity, but NADPH-diaphorase positive fibers and Fos-immunoreactive neurons were consistently co-distributed in the locus coeruleus, parabrachial nucleus, nucleus tractus solitarius and spinal trigeminal nucleus caudalis. These findings demonstrate that nitroglycerin administration activates a selective group of neurons which are a source of nitric oxide or which are in close proximity with neuronal processes containing nitric oxide synthase, and suggest that the nitric oxide synthase synthesizing pathway may be involved at various levels in the central effect of nitroglycerin.
 ...
PMID:NADPH-diaphorase activity and Fos expression in brain nuclei following nitroglycerin administration. 857 45

The influence of nitric oxide on human sperm hyperactivation and capacitation, as well as its mechanism of action and its possible origin from spermatozoa were studied. Percoll-washed spermatozoa from healthy volunteers were incubated in Ham's F-10 medium supplemented or not with the nitric oxide-releasing agents, diethylamine-NONOate or spermine-NONOate, in combination or not with superoxide dismutase or catalase (scavengers for the superoxide anion and for hydrogen peroxide, respectively), or with sodium nitrate, sodium nitrite, or preincubated NONOates. Sperm hyperactivation, capacitation, and nitric oxide synthase activity were determined. High concentrations (0.3 to 1 mM) of NONOates reduced sperm motility. However, a lower concentration (0.1 mM) of the two NONOates had no effect on the percentage of sperm motility or of hyperactivation but resulted in a significant increase in sperm capacitation (24% +/- 4%) when compared to that of control spermatozoa (Ham's F-10 alone, 12% +/- 2%). Nitric oxide released by the NONOates appeared responsible for this effect because sodium nitrate or nitrite or preincubated NONOates (to exhaust the formation of nitric oxide) had no influence on sperm capacitation. Catalase, but not superoxide dismutase, abolished the capacitating action of the NONOates. No nitric oxide synthase activity was detected in spermatozoa, whether they were in their basal state or already capacitated. Furthermore, the nitric oxide synthetase inhibitor L-NG nitroarginine methyl ester did not block sperm capacitation induced by fetal cord serum ultrafiltrate. It is therefore concluded that, although spermatozoa do not possess detectable nitric oxide synthase activity, low levels of nitric oxide induce human sperm capacitation, and this action likely involves hydrogen peroxide.
 ...
PMID:Low levels of nitric oxide promote human sperm capacitation in vitro. 857 82

Dietary supplementation of L-arginine, the precursor of endogenous NO, has been shown to enhance endothelial function in the cholesterol-fed rabbits. However, the mechanism by which dietary L-arginine accomplishes these effects has been unclear. In the present study we have assessed the plasma concentrations of L-arginine and of asymmetrical dimethylarginine (ADMA), a known endogenous inhibitor of NO synthase, in cholesterol-fed rabbits with or without dietary supplementation of L-arginine. Urinary nitrate excretion rates were assessed as an index of endogenous NO formation. Plasma L-arginine levels were not different between control and cholesterol-fed rabbits, but they were elevated nearly threefold in rabbits fed cholesterol + L-arginine. Plasma ADMA concentration increased about two-fold in hypercholesterolemia, but was unaffected by dietary L-arginine. Thus, dietary L-arginine elevated the plasma L-arginine/ADMA ratio above the normal level, and partly restored urinary nitrate excretion, which was decreased by hypercholesterolemia. We conclude that elevation of the L-arginine/ADMA ratio may at least partly explain the restored NO formation by exogenous L-arginine in hypercholesterolemia.
 ...
PMID:Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. 860 33

NO is produced during cardiac allograft rejection by expression of inducible NO synthase (iNOS) in the rejecting heart. Recent evidence indicates that NO modulates vascular permeability under both physiological and pathophysiological conditions. The present study explored the effects of early acute cardiac allograft rejection, and specifically the effects of NO, on myocardial and systemic vascular barrier function using a quantitative double-tracer permeation method in a rat cardiac transplant model. Early allograft rejection increased albumin permeation twofold to fivefold in the allograft heart and systemic vasculature (brain, lung, sciatic nerve, diaphragm, retina, muscle, kidney, and uvea) compared with isografts and controls. There were no detectable differences in regional blood flow or hemodynamics, suggesting that increased albumin permeation resulted from increased vascular permeability. iNOS mRNA was expressed in the allograft heart and native lung and was associated with increased serum nitrite/nitrate levels. iNOS inhibition with aminoguanidine prevented or attenuated allograft heart and systemic vascular barrier dysfunction and reduced allograft serum nitrite/nitrate levels to isograft values. Aminoguanidine did not affect the mild histological changes of rejection present in allografts. These data demonstrate the novel observations that (1) endothelial barrier function is compromised in the systemic vasculature, particularly in the brain, remote from the site of allograft rejection; (2) allograft vascular barrier dysfunction is associated with increased NO production and iNOS mRNA expression in the affected tissues (eg, native lung and grafted heart); and (3) inhibition of NO production by iNOS prevents vascular barrier dysfunction in the allograft heart and systemic vasculature.
 ...
PMID:Inhibition of inducible nitric oxide synthase prevents myocardial and systemic vascular barrier dysfunction during early cardiac allograft rejection. 862 May 96

Short-term infusions of angiotensin II (Ang II) increase renal vascular resistance and thereby endothelial shear stress and nitric oxide (NO) release. Prolonged stimulation of Ang II can decrease the expression of NO synthase isoforms in the macula densa, but prolonged increases in shear stress can increase transcription of endothelial NO synthase. Therefore, we designed these studies to test the hypothesis that Ang II exerts time-dependent effects on renal NO generation as assessed from renal excretion of nitrate and nitrite, percent increases in renal vascular resistance during inhibition of NO synthase with intravenous NG -nitro-L-arginine methyl ester (L-NAME), or decreases in renal vascular resistance during stimulation of endothelial NO synthase with intravenous acetylcholine. Rats were tested during graded short-term (30 to 90 minutes intravenous) or prolonged (5 to 6 days subcutaneous) Ang II infusions that led to dose-dependent increases in blood pressure and renal vascular resistance and reductions in renal blood flow. Captopril was administered for 3 to 4 days to suppress Ang II generation. The renal excretion of nitrate and nitrite was increased during short-term Ang II infusions (from 205 +/- 22 to 331 +/- 58 pmol.min-1, P < .05) but was unchanged during prolonged Ang II infusion (control group, 197 +/- 33 versus Ang II, 245 +/- 42 pmol.min-1, P=NS). The percent increase in renal vascular resistance with L-NAME was potentiated dose dependently by short-term but not long-term Ang II infusions. The increase in renal vascular resistance with L-NAME in control rats without Ang II infusions was +150 +/- 13%. At an Ang II infusion of 200 ng.kg-1.min-1, the L-NAME-induced percent increase in renal vascular resistance was significantly (P < .01) increased compared with controls in short-term Ang II-infused rats (+369 +/- 70%) but was not significantly different in prolonged infused rats (+190 +/- 33%). Intravenous acetylcholine caused dose-dependent renal vasodilation that was not significantly changed in rats receiving short-term intravenous Ang II but was significantly (P < .005) potentiated in those receiving prolonged Ang II infusions (change in renal vascular resistance with acetylcholine at 10 micrograms.kg-1.min-1 versus control, -21.5 +/- 5.0%; with short-term Ang II, -24.9 +/- 4.5%; with long-term Ang II, -52.1 +/- 7.2%). In conclusion, short- and long-term Ang II infusions caused equivalent changes in blood pressure and renal blood flow and hence presumably equivalent increases in endothelial shear stress. However, only short-term Ang II infusions increased NO generation and the dependence of the renal circulation on NO, whereas acetylcholine-induced NO release was enhanced selectively during long-term Ang II infusions. This suggests that during long-term Ang II, renal NO release may become uncoupled from shear stress yet remains highly responsive to receptor-mediated stimulation.
 ...
PMID:Role of nitric oxide in short-term and prolonged effects of angiotensin II on renal hemodynamics. 862 Dec 13

The ex vivo tissue concentration of nitrite and nitrate (NOx) was found to correlate closely with the activity of nitric oxide synthase (NOS; EC 1.14.13.39) in various brain regions. Systemic administration of the nonselective NOS inhibitor N omega-nitro-L-arginine (L-NA) at doses that completely inhibited both central and peripheral NOS, depleted whole-brain and CSF NOx by up to 75% but had no effect on plasma NOx. Selective inhibition of central NOS by intracerebroventricular administration of L-NA methyl ester produced similar decreases in levels of whole-brain NOx. A residual concentration of NOx of 10-15 microM remained in all brain regions even after complete inhibition of brain NOS. Brain NOx content decreased rapidly and in parallel with the inhibition of brain NOS. The ex vivo measurement of levels of brain NOx was found to reflect the in vivo efficacy of several different types of NOS inhibitor: L-NA, N omega-monomethyl-l-arginine, and 7-nitroindazole. Intraperitoneal administration of the NOS substrate L-arginine increased brain NOx concentrations by up to 150% of control values. These results demonstrate that the ex vivo measurement of levels of brain tissue NOx is a rapid, reliable, and straightforward technique to determine NOS activity in vivo. This method can be used to assess both the regional distribution and the degree of inhibition of NOS activity in vivo.
 ...
PMID:Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. 862 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>