Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is involved in blood pressure regulation, and its synthesis is inhibited by methylarginines. It has been hypothesized that one of these, asymmetrical dimethylarginine (ADMA), may contribute to dialysis-associated hypertension because it accumulates in the plasma of hemodialysis (HD) patients in a concentration high enough (4 mumol/L) to inhibit NO synthesis in experimental model systems. A precolumn HPLC technique was used to quantify methylarginines (ADMA and symmetrical dimethylarginine [SDMA]) in plasma from HD patients before and after dialysis, from continuous ambulatory peritoneal dialysis (CAPD) patients, and from healthy subjects. Plasma ADMA concentrations were 0.59 +/- 0.22 (SD) mumol/L in HD patients predialysis (n = 19) and 0.70 +/- 0.27 mumol/L in CAPD patients (n = 11), versus about half of the concentration in control subjects (0.36 +/- 0.08 mumol/L, n = 7). The concentrations of SDMA (not an inhibitor of NO formation) were approximately four to five times the ADMA concentrations in both HD and CAPD patients, in contrast to a ratio of 1:1 in the control subjects. Methylarginine concentrations were reduced by 23% and 40% postdialysis, as calculated from ADMA and SDMA values, respectively. No significant correlations were observed between ADMA concentrations, on the one had, and blood pressure, creatinine and dialysis dose (Kt/V urea), on the other hand. It is concluded that plasma levels of ADMA are considerably lower than those reported earlier in patients treated with HD and also below the levels that hitherto have been thought to have clinical relevance. The role of ADMA in inhibiting NO in dialysis-associated hypertension is questioned.
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PMID:Serum levels of NG, NG-dimethyl-L-arginine, a potential endogenous nitric oxide inhibitor in dialysis patients. 929 36

Nitric oxide (NO) exerts pleiotroptic anti-atherosclerotic effects in the vascular wall: vasodilation, inhibition of platelet aggregation, elukocyte adhesion, and smooth muscle cell proliferation. Experimental and clinical studies showed that the biological effects of NO are impaired in patients with peripheral arterial occlusive disease. In a cross over study with 77 PAOD patients, we could demonstrate impaired NO formation by measuring the index metabolites of NO, nitrate and cyclic GMP. One possible mechanism of these pathophysiological changes is accumulation of the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). The NO-mediated functions of the vascular endothelium will become increasingly important in the clinic: diagnostically, measuring endothelium-dependent vasodilation may become a risk indicator for the development or progression of cardiovascular disease and for assessing the effects of antiatherosclerotic therapy; therapeutically, treatment strategies will be developed aiming at improving endothelial function. In early clinical studies, administration of L-arginine, the amino acid precursor of endogenous NO, has resulted in increased NO formation rates, which may prove therapeutically effective in the future.
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PMID:[Endothelial dysfunction in peripheral arterial occlusive disease: from basic research to clinical use]. 938 83

Eleven patients with thrombotic thrombocytopenic purpura (TTP) or haemolytic uremic syndrome (HUS) were investigated with respect to plasma concentrations of L-arginine, a substrate for nitric oxide (NO) and asymmetrical dimethyl arginine (ADMA), during active disease and after recovery. Plasma concentration of NO3-, the degradation product of NO, was also analyzed. The patients were treated with fresh-frozen plasma and plasmapheresis. One of the patients had experienced relapses of TTP five times during the preceding year. After treatment with p.o. arginine hydrochloride 1.5 g x 3 was started, no relapse has occurred during a 12-month period. During the active phase the plasma concentration of arginine was low and that of NO3- was very high, indicating a high NO-synthesis rate. The arginine concentration normalized on recovery. Plasma levels of ADMA, was twice normal during active disease, and did not return to normal on recovery. In conclusion, patients with TTP/HUS exhibit signs of activation of the NO-synthesis.
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PMID:The arginine-nitric oxide pathway in thrombotic microangiopathy. 940 11

1. The nature of the membrane channels underlying the membrane conductance changes induced by the nitric oxide (NO) donors, S-nitroso-L-cysteine (NOCys) and sodium nitroprusside (SNP) were investigated in single myocytes isolated from the circular muscle layer of the guinea-pig proximal colon, by use of standard whole-cell and single channel recording techniques. 2. Under voltage clamp, depolarizing steps from -60 mV elicited a rapidly-developing, little-inactivating outward K+ current (IK) at potentials positive to -40 mV (at 20-25 degrees C). The steady-state level (ISS) of this K current increased in amplitude as the step potential was made to more positive potentials. If the depolarizing steps were made from a holding potential of -80 mV an additional rapidly activating and inactivating outward K+ current was also elicited, superimposed on IK. 3. At 20-25 degrees C, NOCys (2.5 microM), SNP (100 microM) and 8-bromo-cyclic GMP (500 microM) increased the amplitude of ISS of IK elicited from a holding potential of -60 mV. In contrast, NOCys (2-5 microM) had little effect on ISS at 35 degrees C. Higher concentrations (> or = 5 microM at 20-25 degrees C and > or = 10 microM at 35 degrees C) of NOCys decreased the peak amplitude (I[Peak]) and ISS of IK in a concentration-dependent manner. This blockade of IK with NOCys was always associated with an increase of the holding current (IHold), due to the activation of a membrane conductance with a reversal potential between 0 and + 30 mV and which was reduced approximately 50% upon the addition of Cd2+ (1 mM). 4. NOCys (2.5 to 10 microM) or SNP (100 microM) increased the activity of large conductance Ca2+-activated (BK) K' channels in both cell-attached and excised inside-out patches, bathed in either a symmetrical high K+ (130 mM) or an asymmetrically K+ (6 mMout: 130 mMin) physiological saline. Increases in BK channel activity in NOCys (10 microM) or SNP (100 microM) were associated with an increase in the probability of BK channel opening (N.Po), and with a negative shift of the plots of ln(N.Po) against the patch potential, with little change in the slopes of these plots. In cell-attached patches, the increase in N.Po with NOCys was often associated with a decrease in the BK single channel conductance. 5. In both cell-attached and excised patches, NOCys (2.5 to 10 microM) also activated an additional population of channels which allowed inward current flow at potentials positive to EK. In excised inside-out patches bathed in asymmetrical K+ physiological saline, these single channel currents were 2-3 pA in amplitude at -30 mV and reversed in direction near + 10 mV, even if the NaCl (126 mM) concentration in the pipette solution had been replaced with an equimolar concentration of Na gluconate. 6. Under current clamp, NOCys (2.5 microM) and SNP (100 microM) had variable effects on the membrane potential of colonic myocytes, inducing either a small membrane hyperpolarization of <5 mV, or a slowly-developing membrane depolarization of about 5 mV. In contrast, NOCys (5 microM) produced a transient membrane hyperpolarization which was followed by a large depolarization of the membrane potential to positive potentials. The electrotonic potentials elicited in response to an injection of constant hyperpolarizing current (10 pA for 400 ms) were little changed during the NOCys (5 PM)-induced membrane hyperpolarization, but significantly reduced (to 61% of control) during the periods of membrane depolarization. 7. It was concluded that NOCys and SNP, directly increased the number of active BK channels in the membrane of colonic myocytes which leads to a small rapidly oscillating membrane hyperpolarization. The following rebound depolarization in NOCys arises from both the direct opening of a population of cationic channels and the blockade of voltage- and Ca-activated K+ conductances. Finally, the apamin-sensitive K+channels underlying the initial transient hyperpolarization recorded in the intact proximal colon, in response to nerve-released or directly-applied NO, have yet to be identified at the single channel or whole-cell current level.
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PMID:Effects of nitric oxide donors, S-nitroso-L-cysteine and sodium nitroprusside, on the whole-cell and single channel currents in single myocytes of the guinea-pig proximal colon. 950 92

Neurons in the rat subiculum that are capable of producing nitric oxide were studied by using an antibody to the neuronal isoform of nitric oxide synthase (nNOS). In the light microscope, the staining pattern with the nNOS antibody closely resembled that seen following histochemical processing with nicotinamide adenine dinucleotide phosphate diaphorase. Immunostained neurons were found in all layers, and, in addition, large dendrites in the apical dendrite layer were also immunopositive. Although a few immunolabelled cells had the typical morphology of interneurons, most were found to have the characteristics of pyramidal neurons. In the subiculum, these immunoreactive pyramidal neurons were concentrated mainly in the most superficial cell layers and closest to the CA1 region, but pyramidal neurons in the CA1 layer of the hippocampus were consistently immunonegative. Immunopositive profiles in the subiculum were studied in the electron microscope and compared with unlabelled structures. Ultrastructural criteria suggest that both pyramidal and nonpyramidal subicular neurons are immunopositive for nNOS. Large, spiny dendrites and smaller, varicose dendrites were found to be immunoreactive for nNOS. Vesicle-containing profiles were probably presynaptic axons, and immunopositive boutons were seen to make symmetrical and asymmetrical synaptic contacts.
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PMID:Light and electron microscopic study of neuronal nitric oxide synthase-immunoreactive neurons in the rat subiculum. 960 72

Acute ischaemic stroke is characterised by reductions in local cerebral blood flow (CBF) and activation of circulating platelets and leucocytes. Nitric oxide is a vasodilator and can inhibit these circulating cells. The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a spontaneous nitric oxide donor, was administered at a dose which caused a 10 mm Hg fall in mean arterial blood pressure (MABP) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects. Platelet function (whole blood aggregation and flow cytometry) was assessed before and during SNP administration. Changes in regional CBF were measured using single photon emission computerised tomography (SPECT) scanning. SNP significantly reduced platelet aggregation in both the patient and control subject groups. Equally, the expression of platelet adhesion molecules P-selectin (CD62) and glycoprotein (GP) GP IIIa (CD61) were significantly reduced in both groups. GP Ia (CDw49b) expression was significantly attenuated in the patient but not in the control group. Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients. A total of 24 regions of asymmetrical perfusion were examined, pre-SNP (median (SQR)), 0.68 (0.14) vs. peri-SNP 0.78 (0.17), 2p = 0.065. SNP, given at a dose which reduced MABP by 10 mm Hg, significantly inhibited platelet aggregation and adhesion molecule expression. Improved regional CBF was seen in some patients. SNP is a candidate therapeutic agent for patients with acute ischaemic stroke and warrants further study.
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PMID:Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischaemic stroke. 961 99

In the adult frog, structural asymmetry of the left dorsal habenula in respect to the right counterpart has been repeatedly documented in previous studies. In the present investigation, histochemical expression of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the habenulae of the developing and adult Rana esculenta. In tadpoles and during metamorphosis, selective neuropil staining was consistently found within a lateral compartment of the medial subnucleus of the left dorsal habenula. The staining was still present in the same location, but much less intense, in the mature frog, indicating that the neurochemical pattern observed during development was at least in part transient. Thus, the present data point out a peculiar neurochemical pattern of the habenular asymmetry in the frog, suggesting that nitric oxide may be involved in the developmental shaping which leads to an asymmetrical configuration of the habenulae. In addition, NADPH-diaphorase-positive cells were detected in the frontal organ (the extracranial component of the pineal complex in strict relationship with the habenulae in the frog), and labeled fibers were found in the frontal nerve, which arises from the frontal organ. This latter finding supports the postulated relationship of the habenular asymmetry with the occurrence of the frontal organ. The finding of NADPH-diaphorase histochemical reactivity confined to a distinct portion of the medial subnucleus of the left dorsal habenula prompted a reexamination of the cytoarchitecture of the developing and mature habenular complex in the frog. The bicompartmentalization detected with histochemistry in the medial subnucleus of the left dorsal habenula of the developing and adult frog was fully supported by the study of Nissl-stained epithalamic sections. These data point out that the left-right structural differences of the frog habenular complex are more complex than previously believed, and may be subserved by chemically regulated developmental processes.
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PMID:Nitric oxide synthase activity reveals an asymmetrical organization of the frog habenulae during development: A histochemical and cytoarchitectonic study from tadpoles to the mature Rana esculenta, with notes on the pineal complex. 1041 78

Whether L-Arginine (L-ARG) ameliorates or aggravates renal function and histopathological changes in several models of renal disease remains controversial as L-ARG is the substrate for nitric oxide (NO) synthase as well as the precursor of proline and polyamines which cause renal fibrosis. These ambiguous results might be attributed to differences in the dose and period of L-ARG administration and the animal model used in each observation. Therefore, we tested the dose-dependent effect of L-ARG on mean blood pressure (MBP), 24-hour urinary excretion of protein (UP), NO metabolites (NO2(-) + NO3-) and cyclic GMP (cGMP), plasma asymmetrical dimethylarginine (ADMA), glomerular sclerosis index (SI) and % interstitial fibrosis area (%INT) in 5/6 nephrectomized SD rats. These 5/6 nephrectomized SD rats were divided into 4 groups: 1. L-ARG 0.2 g/kg/day (0.2 g ARG), 2. L-ARG 1 g/kg/day (1 g ARG), 3. L-ARG 2 g/kg/day (2 g ARG), 4. No administration of L-ARG(ARG(-)). Compared with ARG(-)MBP, UP and ADMA were significantly decreased and NO2(-) + NO3-, cGMP were significantly increased in the 0.2 g ARG. SI group and %INT were significantly increased in the 2 g ARG group and decreased in the 0.2 g ARG group. A small dose of L-ARG ameliorated glomerulosclerosis and interstitial fibrosis while a larger dose did not. SI, %INT and ADMA were inversely correlated with NO2(-) + NO3-. These data suggested that renal NO synthesis might attenuate glomerulosclerosis and interstitial fibrosis and the rise in ADMA and L-ARG might cause the decrease in NO.
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PMID:[Paradoxical effect of L-arginine on nitric oxide (NO) synthesis and histopathological changes in 5/6 nephrectomized SD rats]. 1065 23

Gastrin is a hormone regulating gastric acid secretion and the growth of the gastrointestinal epithelium. It is expressed by endocrine tumors and by adenocarcinomas of the gastroenteropancreatic region and may represent an autocrine tumor growth factor. Gastrin is also implicated in the genesis of peptic ulcer disease both in conjunction with H. pylori infections and with gastrin-producing tumors. The secretion and expression of gastrin are under the paracrine control of somatostatin, produced by D cells situated in close contact with gastrin-producing G cells. D cells also contain neuronal nitric oxide synthase and appear to regulate apoptosis of G cells by paracrine release of nitric oxide. Both G and D cells are derived from a common multihormonal precursor cell present in the regenerative (isthmus) region of the gastric units. The precursor cells have been suggested to undergo asymmetrical divisions resulting in gastrin- and somatostatin-producing daughter cells that remain in paracrine contact during their migration into the glands. The precursor cells also give rise to the third main antropyloric endocrine cell type; the serotonin-producing EC cell. The maturation of all of these cell types is regulated by a number of transcription factors containing homeobox motifs (Pdx-1, Pax 4 and 6, Isl-1, Nkx6.1). Many of these also regulate the development of the central nervous system and the pancreas. The use of different combinations of these factors for regulating the expression of different hormones may explain the phenomenon of abberant hormone expression during development and carcinogenesis and the occurrence of multihormonal cells.
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PMID:Developmental biology of gastrin and somatostatin cells in the antropyloric mucosa of the stomach. 1070 44

Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines, bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane interaction can induce production of these mediators. HD can also induce changes of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of this study was to investigate the effect of HD, using cuprophane (C, polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha), bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was similar with the three membranes. Cuprophane HD induced a significant increase in i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No changes were found in PAN and SPAN HD. The TNF-alpha values increased significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes of bradykinin concentration were found during HD. A significant decrease of ADA and nitrate levels was observed during HD with three membranes. No significant correlation was found between percentage increase in i-NOS activity and the changes in other parameters. These findings suggest that HD with bioincompatible membranes can induce activation of cellular i-NOS.
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PMID:[L-arginine-nitric oxide pathway in hemodialysis]. 1091 3


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