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

The most fundamental aspect of the cerebral circulation is the well-described coupling of cerebral metabolic activity and cerebral blood flow. A number of substances have been proposed to link flow and metabolism, including K+, pH and adenosine. In the alpha-chloralose anaesthetised cat we studied simultaneously cerebral neuronal activity and local blood flow to attempt to dissociate the two and thus determine the coupling substance. Neuronal activity was determined by monitoring unit firing in the parietal cortex with tungsten in glass microelectrodes while local cerebral blood flow in the same area was monitored continuously using laser Doppler flowmetry. To initiate an increase in metabolic activity and, pari passu, blood flow spreading depression was elicited by needle stick injury. Spreading depression when initiated causes a wave of depolarization, measured as an increased firing rate and associated marked (400 +/- 95%) increase in local cerebral blood flow. Intravenous administration of NG-nitro-L-arginine methyl ester (1-NAME), a potent nitric oxide synthase inhibitor, produced a complete blockade of the hyperemia associated with spreading depression but no change in either resting cell firing or spreading depression-evoked increases in firing rate. These data demonstrate at least for spreading depression-elicited increases in metabolic activity, that nitric oxide (NO) is a key coupling compound that links changes in cerebral blood flow and metabolism. These data imply that NO may have a more general role in flow/metabolism coupling and further studies in other situations are required to determine the extent to which NO is responsible for this fundamental cerebrovascular phenomenon.
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PMID:Nitric oxide synthesis couples cerebral blood flow and metabolism. 146 53

There is increasing evidence that nitric oxide (NO) plays a role within the central nervous system as a novel messenger. Neuronal culture work suggests NO to be involved specifically in mediating actions of angiotensin II (ANG). The present study examined the potential role of NO within the paraventricular nucleus (PVN), a structure involved in mediating the cardiovascular changes initiated by activation of the subfornical organ (SFO). The pressor response to stimulation of SFO, which can be divided into a short (SD) and long duration (LD) component was enhanced following administration of an NO synthase inhibitor (L-NAME) (SD control: 101 +/- 4 vs. post L-NAME: 145 +/- 10 mmHg.s (P < 0.05); LD control: 387 +/- 167 vs. post L-NAME: 1737 +/- 617 mmHg.s (P < 0.05)). This effect was specific to activation of SFO efferents as the blood pressure responses to either, stimulation of PVN, or systemic administration of vasopressin were not potentiated by administration of L-NAME. These findings suggest that NO may be acting within PVN to inhibit further release of ANG, thereby attenuating the cardiovascular response to stimulation of SFO.
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PMID:Angiotensin II neurotransmitter actions in paraventricular nucleus are potentiated by a nitric oxide synthase inhibitor. 751 40

Gene mutations of superoxide dismutase (SOD) have been discovered in familial amyotrophic lateral sclerosis (ALS). Neuronal nitric oxide synthase (NOS), endothelial NOS and 3-nitrotyrosine immunoreactivities are selectively increased in the spinal motoneurons of sporadic ALS. Other study suggests that 3-nitrotyrosine immunoreactivity is enhanced in the spinal motoneurons of sporadic and familial ALS patients. The hypothesis is postulated that increased production of radical species, such as superoxide and peroxynitrite, may cause motoneuron degeneration in ALS. There are increased amounts of nitric oxide and SOD hypoactivities in the brain and spinal cord of wobbler mice. NOS is also induced in the vacuolated spinal motoneurons or axons in this animal. Free radicals might contribute to the pathogenesis of wobbler mouse motoneuron disease. Lecithinized SOD treatment has retarded the progression of this disease. This evidence allowed us to determine whether NOS inhibitors delay progression of wobbler mouse motoneuron disease. After clinical diagnosis at age 3-4 weeks, wobbler mice were injected with intraperitoneal non-selective NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), two doses of neuronal NOS inhibitor, 7-nitroindazole (5 or 50 mg/kg) or a vehicle solution, daily for 4 weeks in a blind fashion. In comparison with vehicle, 7-nitroindazole-treated mice potentiated grip strength and attenuated deformities in the forelimbs. 7-Nitroindazole treatment increased the biceps muscle weight, reduced denervation muscle atrophy, and suppressed degeneration of spinal motoneurons. To a lesser degree, L-NAME-treated mice displayed slowed progression of disease. The present studies indicate that neuronal NOS inhibitor may be a candidate for promising therapy in lower motoneuron disease or motor neuropathy.
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PMID:Neuronal nitric oxide synthase inhibitor, 7-nitroindazole, delays motor dysfunction and spinal motoneuron degeneration in the wobbler mouse. 980 11

Nitric oxide (NO) may subserve different functions in different central neurons subjected to axotomy. The difference may depend on whether the neurons basally express neuronal nitric oxide synthase (nNOS), a biosynthetic enzyme of NO. This is supported by our previous finding that suggests the differential role of NO in neurons of nucleus dorsalis (ND) and red nucleus (RN) which have different basal expression of nNOS. This study aimed to establish firmly the functions of NO, as revealed by nNOS immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, by the administration of endogenous NO donor, l-arginine (l-arg), and NOS inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME). To relate the role of NO to glutamate receptors (GluR), the distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) in the two nuclei were revealed by immunohistochemical techniques. nNOS immunoreactivity was void in ND neurons, but expressed weakly in the RN normally. It was induced in ipsilateral ND neurons and upregulated on both sides of RN after spinal cord hemisection. Neuronal loss in the ipsilateral ND was augmented by l-arg, but reduced by l-NAME. In the contralateral RN, l-arg attenuated neuronal loss. NMDAR1 was present in most neurons in ND. After axotomy, some NMDAR1 immunoreactive neurons of the ipsilateral ND were induced to express NOS, whereas RN neurons showed strong staining for NMDAR1 and all the AMPA subunits. Most of the NOS-positive neurons in the RN were coexistent with GluR2 in normal rats and those subjected to axotomy. The present data demonstrated that NO exerted neurodestructive function in the non-NOS-containing ND neurons characterized by NMDAR as the predominant glutamate receptor. NO might be beneficial to the NOS-containing RN neurons. This could be attributed to the presence of GluR2. Possible diverse synthesizing pathways of NO in two different central nuclei were suggested from the observation that NOS was colocalized with NADPH-d in ND neurons, but not in RN neurons.
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PMID:Neuroprotective and neurodestructive functions of nitric oxide after spinal cord hemisection. 1068 69

Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of nNOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day) for 1 week, respectively. L-NAME treatment did not change COX-2 expression and conversely rofecoxib treatment did not change nNOS expression in the kidney cortex under any experimental conditions. L-NAME but not rofecoxib attenuated renin mRNA levels. Rofecoxib markedly reduced renal prostanoid excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other.
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PMID:Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency. 1121 Nov 8

1. In normal mice, the distribution of adrenergic, cholinergic, some peptidergic, and neuronal nitric oxide synthase (nNOS)-containing nerves were investigated. Functional in vitro correlates were obtained. An in vivo model was developed in which erectile haemodynamics in response to drugs or nerve-stimulation were studied. 2. Immunoreactivities for vesicular acetylcholine transporter protein (VAChT), nNOS-, and vasoactive intestinal polypeptide (VIP), co-existed in nerve fibres and terminal varicosities. Immunoreactivities for neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were found in the same nerve structures. 3. Chemical sympathectomy abolished TH- and NPY-IR nerve structures in cavernous smooth muscle bundles. The distribution of calcitonin gene-related peptide (CGRP)-, nNOS-, VAChT- and VIP-IR nerve structures was unchanged. 4. In endothelial cells of the central and helicine arteries, veins and venules, intense immunoreactivity for endothelial NOS (eNOS) was observed. No distinct eNOS-IR cells were found lining the cavernous sinusoids. 5. In vitro, nerve-induced relaxations were verified, and endothelial NO/cyclic GMP-mediated relaxant responses were established. VIP and CGRP had small relaxant effects. A functioning adenylate cyclase/cyclic AMP pathway was confirmed. 6. Neuronal excitatory responses were abolished by prazosin, or forskolin. VIP and CGRP counteracted contractions, whereas NPY and scopolamine enhanced excitatory responses. 7. In vivo, erectile responses were significantly attenuated by L-NAME (50 mg kg(-1)) and facilitated by sildenafil (200 microg kg(-1)). 8. It is concluded that the mouse is a suitable model for studies of erectile mechanisms in vitro and in vivo.
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PMID:Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum. 1125 Aug 85

Neuronal damage in glutaryl-CoA dehydrogenase deficiency (GDD) has previously been addressed to N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity of the accumulating neurotoxic metabolite 3-hydroxyglutarate. However, acute encephalopathic crises in GDD patients are typically precipitated by febrile illness or even routine vaccinations, suggesting a potentiating role of inflammatory cytokines. In the present study we investigated the effect of interleukin-1beta and interferon-gamma on 3-hydroxyglutarate toxicity in rat cortical astrocyte cultures and neonatal rat hippocampal cultures. A cotreatment of both culture systems with interleukin-1beta and interferon-gamma induced the protein expression of astrocytic inducible nitric oxide synthase (iNOS), resulting in increased nitric oxide (NO) production. Cytokine pretreatment alone had no effect on cell viability but potentiated 3-hydroxyglutarate neurotoxicity. NOS inhibition by aminoguanidine and L-NAME prevented an iNOS-mediated potentiation of 3-hydroxyglutarate neurotoxicity but failed to protect neurons against 3-hydroxyglutarate alone. In contrast, superoxide dismutase/catalase as well as MK-801 prevented toxicity of 3-hydroxyglutarate alone as well as its potentiation by iNOS, supporting a central role of NMDA receptor stimulation with subsequently increased superoxide anion production. It is concluded that the potentiation of 3-hydroxyglutarate neurotoxicity is most probably due to an induction of astrocytic iNOS and concomitantly increased NO production, enabling enhanced peroxynitrite formation. Thus, we provide evidence for a neuroimmunological approach to the precipitation of acute encephalopathic crises in GDD by inflammatory cytokines.
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PMID:Potentiation of 3-hydroxyglutarate neurotoxicity following induction of astrocytic iNOS in neonatal rat hippocampal cultures. 1142 52

We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a significant decrease in HbO2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.
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PMID:Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits. 1157 52

Neuronal death is a prominent neuropathological component of fetal alcohol syndrome (FAS). Identification of molecular agents and pathways that can ameliorate alcohol-induced cell loss offers possible therapeutic strategies for FAS and potential insight into its pathogenesis. This study investigated the effects of growth factors on cellular survival in alcohol-exposed cerebellar granule cell (CGC) cultures and examined the role of the nitric oxide (NO)-cGMP-PKG (cGMP-dependent protein kinase) pathway in the cell survival-promoting effects of these growth factors. Primary CGC cultures were exposed to 0 or 400 mg/dl ethanol, accompanied by either no growth factor or 30 ng/ml fibroblast growth factor-2 (FGF-2), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF) or epidermal growth factor (EGF). Viable neurons were quantified after 1 day of exposure. Two distinct types of cell survival-promoting effects of growth factors were detectable: (1) a neurotrophic effect, in which the growth factors diminished the background death of neurons that occurred in alcohol-free cultures; and (2) a neuroprotective effect, in which the growth factors diminished alcohol-induced cell death. The various growth factors differed markedly in their patterns of cell survival promotion. While BDNF and FGF-2 exerted both a neurotrophic and a neuroprotective effect, IGF-1 had only a neurotrophic effect and did not protect against alcohol toxicity, and NGF had only a neuroprotective effect and did not diminish background cell death. EGF had neither a neurotrophic nor a neuroprotective effect. In order to determine the role of the NO-cGMP-PKG pathway in the cell survival-promoting effects mediated by growth factors, cultures were exposed to one of several pharmacological inhibitors of the pathway, including NAME, LY83583 and PKG inhibitor. The cell survival-promoting effects of FGF-2, NGF and IGF-1 were all substantially reduced by each of the pathway inhibitors. In contrast, neither the neurotrophic nor the neuroprotective effects of BDNF were altered by any of the pathway inhibitors. Thus, growth factors differ in their patterns of neurotrophic and neuroprotective effects, and they differ in their reliance on the NO-cGMP-PKG pathway. While FGF-2, NGF and IGF-1 all signal their survival-promoting effects through the NO-cGMP-PKG pathway, BDNF does not rely upon this pathway for signal transduction in CGC cultures.
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PMID:FGF-2, NGF and IGF-1, but not BDNF, utilize a nitric oxide pathway to signal neurotrophic and neuroprotective effects against alcohol toxicity in cerebellar granule cell cultures. 1252 73

Treatment with cyclosporin A (CsA) following solid organ transplantations such as heart or liver generally results in bone loss. However, in vitro studies show that CsA inhibits bone resorption. Our previous in vivo animal studies demonstrated that the effects of nitric oxide (NO) on bone are biphasic; at high doses, NO increases bone resorption. In this study, we have examined in an in vitro setting to determine whether the bone loss caused by CsA administration is dependent on the NO-cyclic guanosine monophosphate (cGMP) pathway. Freshly isolated osteoclast-rich neonatal rat long bone marrow cells were added to 100 microM thick dentin sections that had been seeded with neonatal-rat calvarial osteoblasts. These co-cultures were maintained for 48 hrs in a basal medium with CsA (1, 5, and 10 microg/ml), both alone and with either L-Arginine (NO substrate; 10-3M), L-NAME (NO synthase enzyme inhibitor; 10-4M), or the combination of the two. The cultures were then fixed in cold 95% ethanol and stained with tartrate resistant acid phosphatase (TRAP) to identify osteoclasts and sites of osteoclastic resorption. Preparations were analyzed using an automated histomorphometry software package. Scanning electron microscopy affirmed that the areas identified by light microscopy as resorption sites contained osteoclastic lacunae. CsA inhibited bone resorption dose-dependently. CsA at 10 microg/ml produced a 90% inhibition of bone resorption (control = 5.5 -/+2.0%; CsA = 0.64 -/+ 0.09=). L-Arginine reversed this inhibition by 90% (Arg + CsA = 4.23 -/+ 1.57%; CsA = 0.64 -/+ 0.09%). The application of NOS inhibitor L-NAME inhibited bone resorption by 87% (Arg + CsA + L-NAME = 0.55 -/+ 0.14%; Arg + CsA = 4.23 -/+ 1.5%). We conclude that NO-cGMP pathway is involved in the CsA induced bone loss.
J Musculoskelet Neuronal Interact 2000 Dec
PMID:The mechanism of bone resorption by cyclosporin: involvement of the NO-cGMP pathway. 1575 8


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