UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.
...
PMID:Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits. 877 Jan

This experiment examined the effects of nitric oxide (NO) synthase inhibition on brain intracellular pH, regional cortical blood flow, and NADH fluorescence before and during 3 h of focal cerebral ischemia using in vivo fluorescence imaging. Thirty fasted rabbits under 1% halothane were divided into four treatment groups receiving N omega-nitro-L-arginine methyl ester (L-NAME) intravenously at 20 min prior to ischemia (0.1, 1, and 10 mg/kg and 1 mg/kg + 5 mg/kg L-arginine) and two control groups (nonischemic and ischemic). In ischemic controls, brain pH(i), declined to 6.73 +/- 0.03 at 30 min and remained acidotic through the remainder of the ischemic period. In the 0.1 mg/kg group, brain pH(i) fell after 30 min of ischemia to 6.76 +/- 0.05 (p < 0.05), but then improved progressively despite occlusion. In the 1 mg/kg group, brain pH(i), remained normal despite middle cerebral artery (MCA) occlusion. In the 10 mg/kg group and in the combined L-NAME + L-arginine group, pH(i) fell after 30 min of ischemia to 6.81 +/- 0.03 (p < 0.05) and remained acidotic. During occlusion, regional cortical blood flow dropped in a dose-dependent manner. After 3 h of ischemia, regional cortical blood flow was 33.9 +/- 10.9 and 25.1 +/- 8.9 ml/100 g/min at doses of 0.1 and 10.0 mg/kg, respectively, L-NAME treatment did not significantly alter the increased NADH fluorescence that accompanied occlusion. This study shows that L-NAME can prevent intracellular brain acidosis during focal cerebral ischemia independent from regional cortical blood flow changes. This experiment suggests that NO is involved in pH(i) regulation during focal cerebral ischemia.
...
PMID:Nitric oxide synthase inhibition by L-NAME prevents brain acidosis during focal cerebral ischemia in rabbits. 878 44

The role of mitochondrial energy metabolism in glutamate mediated neurotoxicity was studied in rat neurones in primary culture. A brief (15 min) exposure of the neurones to glutamate caused a dose-dependent (0.01-1 mM) increase in cyclic GMP levels together with delayed (24 h) neurotoxicity and ATP depletion. These effects were prevented by either the nitric oxide (.NO) synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (NAME; 1 mM) or by the N-methyl-D-aspartate (NMDA) glutamate-subtype receptor antagonist D-(-)-2-amino-5-phosphonopentanoate (APV; 0.1 mM). Glutamate exposure (0.1 mM and 1 mM) followed by 24 h of incubation caused the inhibition of succinate-cytochrome c reductase (20-25%) and cytochrome c oxidase (31%) activities in the surviving neurones, without affecting NADH-coenzyme-Q1 reductase activity. The rate of oxygen consumption was impaired in neurones exposed to 1 mM glutamate, either with glucose (by 26%) or succinate (by 39%) as substrates. These effects on the mitochondrial respiratory chain and neuronal respiration, together with the observed glutathione depletion (20%) by glutamate exposure were completely prevented by NAME or APV. Our results suggest that mitochondrial dysfunction and impairment of antioxidant status may account for glutamate-mediated neurotoxicity via a mechanism involving .NO biosynthesis.
...
PMID:Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion. 959 99

The interaction between nitric oxide (NO.) and focal cerebral ischemia is multifaceted. Experiments have shown that inhibition of nitric oxide synthase (NOS) either ameliorates or exacerbates focal cerebral ischemia. Recent in vitro experiments have shown that NOS activity is pH-dependent. Previous work from this laboratory has demonstrated that N(G)-nitro-L-arginine-methyl-ester (L-NAME) mitigated cerebral ischemia independent from regional cerebral blood flow (rCBF) changes during moderate focal cerebral ischemia. This study examined the effects of L-NAME inhibition on brain pH(i), rCBF, and NADH redox state during 3 h of severe focal cerebral ischemia. Fifteen fasted rabbits under 1.5% halothane were equally divided into three groups: ischemic controls and two drug groups receiving either 1.0 or 10 mg/kg L-NAME intravenously 30 min prior to ischemia. In the ischemic controls, brain pH(i) declined from 6.95+/-0.04 to 6.60+/-0.05, rCBF declined from 48+/-7 to 10+/-3 ml/100 g/min, and NADH fluorescence increased by 149+/-15% 3 h after onset of ischemia (p<0.01 for all three parameters). L-NAME at either dose did not significantly alter these values. Infarct volume was not significantly different between both the L-NAME treated groups and the ischemic control group. This data suggests that during severe focal cerebral ischemia, NO. mechanisms of injury have a less important punitive role. One possible explanation is that the severity of acidosis secondary to anaerobic metabolism during severe focal cerebral ischemia attenuates NOS activity.
...
PMID:Is intracellular brain pH a dependent factor in NOS inhibition during focal cerebral ischemia? 1067 29

We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)-sensitive flow-induced dilations were significantly impaired (Y: 41+/-8% versus A: 3+/-2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not L-arginine or the TXA(2) receptor antagonist SQ29,548). For lucigenin chemiluminescence, O(2)(.-) generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O(2)(.-) generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O(2)(.-) (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47(phox), p67(phox), Mox-1, and p22(phox) did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.
...
PMID:Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. 1206 18

Sepsis is associated with increased production of reactive oxygen species (ROS); however, the metabolic sources of increased ROS are not well understood. We hypothesized that the recently described nonphagocytic NAD(P)H oxidase system could be an important source of the ROS superoxide anion (O2-) during sepsis, and the interaction of O2- with nitric oxide (NO) may contribute to sepsis-induced vascular Injury. To evaluate this issue, we measured O2- production before and after treatment with lipopolysaccharide (LPS) in rats, who are Inducible NO synthase producers (NOSII) and in pigs, who do not produce NOSII. LPS increased O2- production in aorta from rats from 0.38 +/- 0.07 nmol/mg/10 min to 1.18 +/- 0.23 nmol/mg/10 min, (P = 0.001) in rats, and 0.63 +/- 0.05 nmol/mg/10 min to 1.5 +/- 1.6 nmol/mg/10 min (P = 0.001) in carotid arteries from pigs. Components of NAD(P)H oxidase, including p22(phox), gp91(phox), p47(phox), p67(phox), mRNA and p22(phox), and gp91(phox) proteins were present in rat aorta and aorta and carotid arteries from pigs. Expression mildly increased in rats, but not in pigs. In rats, NADH and NADPH greatly increased O2- production with no difference in untreated versus LPS-treated rats. The addition of L-NAME increased NADH-dependant O2- production from 75 +/- 3 nmol/O2-/mg/10 min to 113 +/- 7 nmoVO2-/mg/10 min in LPS-treated rats, but had no effect in untreated rats. In pigs, the NADH-stimulated O2- production was 43 +/- 8 nmol/mg/10 min before and 63 +/- 4.3 nmol/mg/10 min after LPS even without L-NAME (P < 0.05). In contrast to LPS-treated rats, L-NAME markedly decreased NADH-stimulated O2- production (63 +/- 4 nmol/mg/10 min to 33 +/- 5.6 nmol/mg/10 min, P < 0.01). Luminol-enhanced chemiluminescence was also Increased in porcine carotid arteries after LPS treatment, which is consistent with peroxynitrite formation. Our results indicate that components of NAD(P)H oxidase are present in vessels of pigs and rats and there is substantial NADH-dependent O2- production that is increased after LPS. However, the behavior of NAD(P)H oxidase in NOSII-producing and nonproducing species differs with a reduction of O2- by NO in rats and NO-dependent production in pigs.
...
PMID:Superoxide production in the vasculature of lipopolysaccharide-treated rats and pigs. 1274 95

Hypothermic perfusion of the heart decreases oxidative phosphorylation and increases NADH. Because O(2) and substrates remain available and respiration (electron transport system, ETS) may become impaired, we examined whether reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A fiberoptic probe was placed on the left ventricular free wall of isolated guinea pig hearts to record intracellular ROS, principally superoxide (O(2)(-).), and an extracellular reactive nitrogen reactant, principally peroxynitrite (ONOO(-)), a product of nitric oxide (NO.) + O(2)(-). Hearts were loaded with dihydroethidium (DHE), which is oxidized by O(2)(-). to ethidium, or were perfused with l-tyrosine, which is oxidized by ONOO(-) to dityrosine (diTyr). Shifts in fluorescence were measured online; diTyr fluorescence was also measured in the coronary effluent. To validate our methods and to examine the source and identity of ROS during cold perfusion, we examined the effects of a superoxide dismutase mimetic Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and several agents that impair electron flux through the ETS: menadione, sodium azide (NaN(3)), and 2,3-butanedione monoxime (BDM). Drugs were given before or during cold perfusion. ROS measured by DHE was inversely proportional to the temperature between 37 degrees C and 3 degrees C. We found that perfusion at 17 degrees C increased DHE threefold versus perfusion at 37 degrees C; this was reversed by MnTBAP, but not by l-NAME or BDM, and was markedly augmented by menadione and NaN(3). Perfusion at 17 degrees C also increased myocardial and effluent diTyr (ONOO(-)) by twofold. l-NAME, MnTBAP, or BDM perfused at 37 degrees C before cooling or during 17 degrees C perfusion abrogated, whereas menadione and NaN(3) again enhanced the cold-induced increase in ROS. Our results suggest that hypothermia moderately enhances O(2)(-). generation by mitochondria, whereas O(2)(-). dismutation is markedly slowed. Also, the increase in O(2)(-). during hypothermia reacts with available NO. to produce ONOO(-), and drug-induced O(2)(-). dismutation eliminates the hypothermia-induced increase in O(2)(-).
...
PMID:Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart. 1464 63

The clinical use of the widely used anticancer drug doxorubicin is limited by a dose-dependent cardiotoxicity. Doxorubicin can be reduced to its semiquinone free radical form by nitric oxide synthases (NOS). The release of lactate dehydrogenase (LDH) from doxorubicin-treated neonatal cardiac rat myocytes was used as a model of doxorubicin-induced cardiotoxicity. The NOS inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA) protected myocytes from doxorubicin as did their non-inhibitory enantiomers D-NAME and D-NMMA. Thus, these agents did not protect by inhibiting NOS. L-NAME, which does not act at the reductase domain of NOS, also had no effect on the production of the doxorubicin semiquinone by myocytes. Nitric oxide (NO) EPR spin trapping experiments showed that L-NAME reacted with various biological reducing agents to produce NO. Ascorbic acid was highly effective in reacting with L-NAME to produce NO, while glutathione, NADPH, and NADH were much less effective. Thus, these guanadino-substituted analogs of L-arginine likely protected through their ability to slowly produce NO by reaction with intracellular ascorbic acid. Thus, some caution must be exercised in their use. NO may exert its protective effects either by directly acting as an antioxidant or through some other NO-dependent pathway.
...
PMID:Prevention of doxorubicin-induced damage to rat heart myocytes by arginine analog nitric oxide synthase inhibitors and their enantiomers. 1499 28

Cardioprotection by anesthetic preconditioning (APC) can be abolished by nitric oxide (NO*) synthase inhibitors or by reactive oxygen species (ROS) scavengers. We previously reported attenuated mitochondrial electron transport (ET) and increased ROS generation during preconditioning sevoflurane exposure as part of the triggering mechanism of APC. We hypothesized that NO* and other ROS mediate anesthetic-induced ET attenuation. Cardiac function and reduced nicotinamide adenine dinucleotide (NADH) fluorescence, an index of mitochondrial ET, were measured online in 68 Langendorff-prepared guinea pig hearts. Hearts underwent 30 min of global ischemia and 120 min of reperfusion. Before ischemia, hearts were temporarily perfused with superoxide dismutase, catalase, and glutathione to scavenge ROS or N(G)-nitro-L-arginine-methyl-ester (L-NAME) to inhibit NO* synthase in the presence or absence of 1.3 mM sevoflurane (APC). APC temporarily increased NADH before ischemia, i.e., it attenuated mitochondrial ET. Both this NADH increase and the cardioprotection by APC on reperfusion were prevented by superoxide dismutase, catalase, and glutathione and by N(G)-nitro-L-arginine-methyl-ester. Thus, ROS and NO*, or reaction products including peroxynitrite, mediate sevoflurane-induced ET attenuation. This may lead to a positive feedback mechanism with augmented ROS generation to trigger APC secondary to altered mitochondrial function.
...
PMID:Anesthetic preconditioning: the role of free radicals in sevoflurane-induced attenuation of mitochondrial electron transport in Guinea pig isolated hearts. 1561 50

Successful blastocyst implantation depends on the interaction between cells of maternal endometrium and conceptus, as well as adequate blood supply to the site of blastocyst implantation. Nitric oxide (NO) generally plays a significant role in the local regulation of vascular physiology in a variety of mammalian tissue systems, however, its role in blastocyst implantation and placentation in the primate is not known. The aim of the present study was to examine: (i) NADH-diaphorase activity and expression of three isoforms of nitric oxide synthase (NOS), namely endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS) in pre-implantation stage monkey embryos, morula (n = 4) and blastocyst (n = 10), as well as, in different compartments of conceptus and maternal endometrium at primary implantation sites during lacunar (n = 6) and villous (n = 9) stages of placentation in the rhesus monkey, and (ii) the potential anti-nidatory effect of vaginal administration of NOS inhibitor during the peri-implantation period of conception cycles in rhesus monkeys. Pre-implantation stage blastocysts exhibited marked NADPH-diaphorase activity along with immunopositive iNOS mainly in the inner cell mass. During the lacunar stage, marked eNOS expression was observed in cytotrophoblast cells lining the embryonic cavity. However, cytotrophoblast cells lining villi, forming columns, and constituting anchoring villi expressed all the three isoforms of NOS in villous placenta stage tissue. During the lacunar stage, eNOS and iNOS protein expressions were observed in epithelial and decidual cells of endometrium. As gestation advanced, mRNAs for all three isoforms of NOS were observed to increase in epithelial and decidual cells, however, with no marked change in protein expression. Vaginal administration of a NOS inhibitor (N(G)-nitro-l-arginine methyl ester, L-NAME, 4, 6, and 8 mg/kg body weight or aminoguanidine, AG, 4 mg/kg body weight) during days 6 to 12 after ovulation resulted in pregnancy failure in a higher number of animals (L-NAME: 8 confirmed pregnancies in 25 animals; AG: 2 confirmed pregnancies in 8 animals) compared with control animals (5 pregnancies in 7 animals). It appears that NO may play an important role in the establishment of pregnancy in the rhesus monkey.
...
PMID:Nitric oxide in blastocyst implantation in the rhesus monkey. 1612 39

1 2 Next >>