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

We studied the effects of nitric oxide synthase (NOS) inhibitors and nitric oxide (NO.) donors on ischemia-reperfusion (I/R)-induced microvascular permeability increase in isolated buffer-perfused rat lungs. Microvascular permeability (Kf,c) was significantly increased in lungs subjected to 45 min of ischemia followed by 30 min of reperfusion. Lungs that were pretreated with 300 and 600 microM N omega-nitro-L-arginine methyl ester (L-NAME), 1, 300, and 600 microM NG-monomethyl-L-arginine (L-NMMA), or 600 microM L-N6-(1-iminoethyl) ornithine (L-NIO) still showed significant increases in Kf,c after I/R. Lungs that were pretreated with 5 mM L-NAME or 5 mM N omega-nitro-D-arginine methyl ester showed no increase in Kf,c after I/R. However, both compounds at these concentrations produced significant decreases in perfusate pH. The decreased pH was responsible for the protective effects, since lungs pretreated with 5 mM L-NAME and supplemented with NaHCO3 to prevent the perfusate pH decrease still showed a significant elevation in Kf,c after I/R. In additional experiments, NO.donors were administered to isolated lungs at the onset of reperfusion. Spermine-NO (100 microM) and S-nitroso-N-acetylpenacillamine (300 microM) both prevented the increase in Kf,c associated with I/R. We conclude from these studies that peroxynitrite does not mediate microvascular permeability increase after lung I/R injury in this model, and exogenous NO. does not exacerbate injury; rather, it prevents microvascular damage.
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PMID:Role of nitric oxide in lung ischemia and reperfusion injury. 894 16

The role of endothelin ETA and ETB receptors as well as of nitric oxide (NO) and prostanoids in the effects of endothelin-1 on the coronary circulation was studied in anesthetized goats. Where blood flow in the left circumflex coronary artery (coronary blood flow) (electromagnetically measured), systemic arterial pressure, left ventricle pressure and d P/dt, and heart rate were recorded. Endothelin-1 (0.01-0.3 nmol), intracoronarily injected, produced marked, dose-dependent reductions in basal coronary blood flow, ranging from 5% for 0.01 nmol to 75% for 0.3 nmol; 0.1 and 0.3 nmol endothelin-1 also reduced systolic ventricle pressure and dP/dt. The effects of endothelin-1 on coronary blood flow were diminished during intracoronary infusion of BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp). specific antagonist for endothelin ETA receptors. 2-16 nmol/min) in a dose-dependent way, but not during the infusion of BQ-788 (N-[N-[N-[(2.6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-1-leucyl]-1- (methoxycarbonyl)-D-tryptophyl]-D-norleucine monosodium, specific antagonist for endothelin ETB receptors. 2-4 nmol/min). IRL 1620 (Suc-[Glu9, Ala11.15]endothelin-1-(8-21), specific agonist for endothelin ETB receptors. 0.01-0.3 nmol), intracoronarily injected. slightly reduced basal coronary blood flow only when 0.1 and 0.3 nmol were applied (maximal reduction about 25%); 0.3 nmol IRL 1620 also reduced systolic ventricle pressure and dP/dt. The effects of IRL 1620 were not modified by BQ-123 or BQ-788. NG-nitro-1-arginine methyl ester (L-NAME, inhibitor of NO synthesis, 47 mg/kg by i.v. route) reduced resting coronary blood flow by 10% and increased mean systemic arterial pressure and systolic ventricle pressure by 22 and 20%. respectively, without changing systolic ventricle dP/dt and heart rate. With L-NAME, the reductions of coronary blood flow by endothelin-1 were potentiated (P < 0.05), and those by IRL 1620 were not changed (P > 0.05). Meclofenamate (cyclooxygenase inhibitor, 4-6 mg/kg by i.v. route) modified neither the basal values of hemodynamic variables nor the coronary effects of endothelin-1 and IRL 1620. Therefore, endothelin-1 produces marked coronary vasoconstriction, which may be mediated by endothelin ETA receptors, with no participation of endothelin ETB receptors. NO, but not prostanoids, may produce a basal coronary vasodilator tone and may inhibit endothelin-1-induced coronary vasoconstriction. Also, it is suggested that the coronary vasoconstriction by endothelin-1 may impair cardiac performance due to heart ischemia.
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PMID:Coronary vasoconstriction by endothelin-1 in anesthetized goats: role of endothelin receptors, nitric oxide and prostanoids. 896 Aug 82

Endothelial driving factors pathophysiologically affect the regulation of coronary circulation. To investigate the regulation of vascular function by endothelium-derived relaxing factor (EDRF) and endothelial cells, endothelium-dependent relaxation impairment was studied in acute ischemia-reperfusion injury in large coronary artery and coronary microvasculature. EDRF (NO) production and release were inhibited due to ischemia-reperfusion injury to the endothelium of large coronary arteries. There was an increased sensitivity selective to ET-1 in large coronary arteries exposed to ischemia and reperfusion. Reduced endothelium-dependent relaxation and augmented ET-1 sensitivity in large coronary arteries suggest the existence of spasmogeneity in reperfused blood vessels. Ischemia and reperfusion also brought about various morphological and functional changes in the reperfused coronary microvasculature. Edema of perivascular interstitium and endothelial cells was the main observation and caused a decrease in the ability of the microvascular bed to dilate because of extravascular compression. To examine the long-term suppression of NO synthesis accompanying endothelial dysfunction, the long-term reactions of coronary arteries and myocardium due to chronic inhibition of NO synthesis by continuously infused L-NAME was investigated. Endothelial cell impairment, proliferation and disarrangement of medial smooth muscle cells, microvascular injury due to platelet thrombi and increased perivascular fibrous tissue were found in rat coronary arteries. Myocardial fibrosis due to coronary microvascular injury was observed. These changes in coronary arterial and myocardial structure were suppressed by ACE inhibitors. Therefore, ACE inhibitors are useful in the treatment of coronary microvascular impairments.
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PMID:Regulation and failure of coronary circulation. 897 73

Ischemia and reperfusion may damage myocytes and endothelium in jeopardized hearts. This study tested whether (1) endothelial dysfunction (reduced nitric oxide release) exists despite good contractile performance and (2) supplementation of blood cardioplegic solution with nitric oxide precursor L-arginine augments nitric oxide and restores endothelial function. Among 30 Yorkshire-Duroc pigs, 6 received standard glutamate/aspartate blood cardioplegic solution without global ischemia. Twenty-four underwent 20 minutes of 37 degrees C global ischemia. Six received normal blood reperfusion. In 18, the aortic clamp remained in place 30 more minutes and all received 3 infusions of blood cardioplegic solution. In 6, the blood cardioplegic solution was unaltered; in 6, the blood cardioplegic solution contained L-arginine (a nitric oxide precursor) at 2 mmol/L; in 6, the blood cardioplegic solution contained the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME) at 1 mmol/L. Complete contractile and endothelial recovery occurred without ischemia. In jeopardized hearts, complete systolic recovery followed infusion of blood cardioplegic solution and of blood cardioplegic solution plus L-arginine. Conversely, contractility recovered approximately 40% after infusion of normal blood and blood cardioplegic solution plus L-NAME. Postischemic nitric oxide production fell 50% in the groups that received blood cardioplegic solution and blood cardioplegic solution plus L-NAME but was increased in the group that received blood cardioplegic solution L-arginine. In vivo endothelium-dependent vasodilator responses to acetylcholine recovered 75% +/- 5% of baseline in the blood cardioplegic solution plus L-arginine group, but less than 20% of baseline in other jeopardized hearts. Endothelium-independent smooth muscle responses to sodium nitroprusside were relatively unaltered. Myeloperoxidase activity (neutrophil accumulation) was similar in the blood cardioplegic solution (without ischemia) and blood cardioplegic solution plus L-arginine groups (0.01 +/- 0.002 vs 0.013 +/- 0.003 microgram/gm tissue). Myeloperoxidase activity was raised substantially to 0.033 +/- 0.002 microgram/gm after exposure to normal blood and to 0.025 +/- 0.003 microgram/gm after infusion of blood cardioplegic solution and was highest at 0.053 +/- 0.01 microgram/gm with exposure to blood cardioplegic solution plus L-NAME in jeopardized hearts. The discrepancy between contractile recovery and endothelial dysfunction in jeopardized muscle can be reversed by adding L-arginine to blood cardioplegic solution.
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PMID:Endothelial stunning and myocyte recovery after reperfusion of jeopardized muscle: a role of L-arginine blood cardioplegia. 904 Jun 33

Several peptide growth factors, including EGF, are known to protect endothelium from oxygen-related damage or ischemia-reperfusion, in vitro experiments show that such protective effect involves endogenous endothelium-related factors like nitric oxide and prostanoids. However, in vivo demonstrations of a possible role in related vascular diseases are lacking. In our experiments, human EGF and fraction C, a 3-10 kDa oligosaccharidic fraction from an aqueous extract of Triticum vulgare, known as growth promoters for several cell types including endothelial cells, were found protective against ischemic necrosis of the mouse tail induced by i.v. k-carrageenin plus endothelin-1. After i.p. injection, peak activities were observed at 10 micrograms/kg EGF and 2 mg/kg fraction C. Pretreatment with L-NAME reduced protection in a dose-dependent manner. Addition of indomethacin increased the effect of L-NAME, suggesting that both nitric oxide and eicosanoids are involved in the protective effect of EGF and fraction C.
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PMID:Protective action of epidermal growth factor and a fraction from Triticum vulgare extract in mouse tail necrosis. 907 27

Systemic nitric oxide synthase inhibition (NOSI) decreases cerebral blood flow, which may worsen ischemic insults. To examine the local effects of NOSI without this confounding effect, we examined the role of a locally administered NOSI, NG-nitro-L-arginine-methyl-ester (L-NAME), on neurotransmitter recovery during cerebral ischemia. Rats were assigned to one of three groups: locally administered L-NAME via a striatal microdialysis probe (n = 11), systemic L-NAME (n = 5), or control (n = 11). Temporary global forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion. L-NAME resulted in decreases of basal aspartate (ASP; 74% of basal) and glutamate (GLU; 60% of basal) recovery. While systemic L-NAME caused significant increases in ischemic ASP and GLU recovery (by 224% and 110%, respectively, compared with ischemic controls), local NOSI administration resulted in a significant attenuation of peak ASP, GLU, glycine, and gamma-aminobutyric acid recovery (43%, 38%, 53%, and 72%, respectively, compared with ischemic controls). We conclude that local NOSI attenuated ischemic neurotransmitter recovery during ischemia/reperfusion. Our results emphasize the importance of the systemic effects of NOSI and suggest both deleterious and beneficial effects of NOSI during ischemia/reperfusion.
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PMID:Modulation of ischemic excitatory neurotransmitter and gamma-aminobutyric acid release during global temporary cerebral ischemia by local nitric oxide synthase inhibition. 914 22

Nitric oxide (NO) and adenosine are important mediators in the regulation of coronary vascular tone and are released into the interstitium from the vascular endothelium and myocardium, respectively. The roles of these autacoids in the regulation of coronary flow in the basal and reactive hyperemic states were examined in Langendorff rabbit hearts perfused with oxygenated Krebs-Henseleit solution at 37 degrees C and 110 mmHg pressure. Instantaneous perfusion pressure-flow relationships were analyzed to derive coronary conductance both in the basal state and during the early phase of reperfusion (hyperemic state). N omega-nitro-L-arginine methyl ester (L-NAME) at increasing concentrations (10(-6) to 10(-4) mol/L) (n = 7) and 8-phenyltheophylline (8-PT) at increasing concentrations (10(-9) to 10(-6) mol/L) (n = 7) were applied to assess the role of NO and adenosine, respectively. L-NAME dose-dependently reduced the coronary conductance in both the basal and early hyperemic states, while 8-PT dose-dependently reduced conductance only in the hyperemic state. Changes in conductance during the early hyperemic phase correlated well with changes in the debt repayment ratio for either L-NAME (r = 0.94) or 8-PT (r = 0.99). These data suggest that a flow-related NO release mechanism regulates the coronary conductance in both the basal and hyperemic states while the metabolic regulation of adenosine release plays a role in the presence of ischemia.
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PMID:Roles of nitric oxide and adenosine in the regulation of coronary conductance in the basal state and during reactive hyperemia. 919 44

To examine if inhibition of nitric oxide (NO) synthesis influences myocardial ischemia-reperfusion injury, male Sprague Dawley rats were administered the NO synthesis inhibitor N -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.) or saline 6 hours prior to excising the heart and aorta. Aortic ring contractile response to norepinephrine (NE) was more pronounced and relaxation in response to acetylcholine was abolished in L-NAME-treated group (P<0.05 vs. saline-treated group), indicating inhibition of NO synthesis in the vascular tissues. In the isolated perfused Langendorff hearts, force of cardiac contraction (FCC) and coronary perfusion pressure (CPP) were higher and coronary flow was lower in the L-NAME-treated group, again suggesting inhibition of NO synthesis. Global ischemia (40 min) followed by reperfusion (30 min) resulted in a decrease in FCC and coronary flow and an increase in CPP in all hearts. Myocardial CK also decreased similarly in all hearts. However, ischemia-reperfusion-induced decline in myocardial superoxide dismutase (SOD) activity and increase in malondialdehyde were prevented in the L-NAME-treated group (P<0.01 vs. saline-treated hearts). Thus treatment with L-NAME with resultant inhibition of NO synthesis does not affect ischemia-reperfusion-induced cardiac dysfunction and injury in the isolated rat hearts, although the reduction in SOD activity and the rise in lipid peroxidation following reperfusion are attenuated.
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PMID:Inhibition of nitric oxide does not affect reperfusion-induced myocardial injury, but it prevents lipid peroxidation in the isolated rat heart. 921 82

We examined the effects of hypoxic/ischemic stress on cerebral arteriolar responses to oxytocin in anesthetized piglets. Pial arteriolar diameters were measured using a cranial window and intravital microscopy. First, we evaluated arteriolar responses to topical application of oxytocin during normoxic conditions. We then determined whether 5-10 min of arterial hypoxia, ischemia, or asphyxia alters oxytocin-induced responses. Arterial hypoxia was produced by inhalation of 7.5% O2-92.5% N2 for 10 min. Ischemia was achieved by increasing intracranial pressure for 10 min. Asphyxia was achieved by turning off the ventilator for 5 min. During normoxic conditions, oxytocin dilated pial arterioles by 9 +/- 1% at 10(-8) and by 16 +/- 1% at 10(-6) mol/l (n = 47, p < 0.05). Arteriolar responses to oxytocin did not change with repeated applications (n = 10). Following hypoxia, dilator effect of oxytocin was not changed at 10(-8) (8 +/- 2%) but it was reduced at 10(-6) mol/l (7 +/- 2%; p < 0.05, n = 8). After asphyxia or ischemia, oxytocin did not dilate arterioles at 10(-8) mol/l, whereas 10(-6) mol/l resulted in a mild vasoconstriction (-4 +/- 3 to -6 +/- 4%, n = 6 and 8). Topically applied superoxide dismutase did not preserve arteriolar responses to oxytocin after asphyxia although the arterioles did not constrict to 10(-6) mol/l oxytocin (n = 5). Dilatation of cerebral arterioles in response to oxytocin was reversed to constriction by N(omega)-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg, i.v.; n = 5) and by endothelial impairment by intra-arterial infusion of phorbol ester (10[-5] mol/l; n = 5). We conclude that the absence of pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates endothelial dysfunction which may be involved in the pathology of perinatal brain injury.
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PMID:Influence of hypoxia/ischemia on cerebrovascular responses to oxytocin in piglets. 925 92

Nitric oxide (NO) is a free radical and was regarded as noxious to life. But recent studies show that NO is an important substance for transcellular signal transduction. It also seems to act as a neurotransmitter in the nervous system. In ischemic nerve tissue a release of glutamate is one of the critical factors that increase neuronal death, and some experiments suggest that NO may be involved in this process. Here we provide evidence that NO provides neuroprotection in ischemic retinas in vivo. Albino rabbits' eyes were subjected to 60 minutes of ischemia by raising intraocular pressure. Before ischemia the eyes were treated intravitreously with the NO-precursor L-arginine, the NO synthase-inhibitor nitro-L-arginine methyl ester hydrochloride (L-NAME), the NO-donor sodium nitroprusside (SNP), or solvent only. The amplitude of the b-wave was measured and the recovery ratio of the b-wave was analyzed hourly after reperfusion. The recovery ratio of b-wave in the eyes with L-arginine and with SNP increased more rapidly than in the controls, while the recovery ratio in the eyes with L-NAME increased in a way similar to that of the controls. These results suggest that NO plays a neuroprotective role in ischemic retina. It may be involved with S-nitrosylation of some proteins, including one of the glutamate receptors, the N-methyl-D-aspertate (NMDA) receptor.
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PMID:[Protective effect of nitric oxide on ischemic retina]. 928 18


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