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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patch-clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG-methyl-L-arginine consistently prevents the induction of long-term depression (LTD) of parallel fibre-mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8-bromoguanosine 3':5' cyclic monophosphate is able to reproduce an LTD-like phenomenon. LTD of parallel fibre-mediated EPSPs also occurs when nitric oxide donors or guanosine 3':5' cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.
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PMID:Long-term depression requires nitric oxide and guanosine 3':5' cyclic monophosphate production in rat cerebellar Purkinje cells. 750 17

The actions of NO synthase inhibitors and indomethacin, a cyclooxygenase inhibitor, on the nonadrenergic noncholinergic (NANC) mechanical responses of cat distal colon were studied in vitro using muscle strips orientated in the axis of the longitudinal muscle layer with pelvic nerves attached. Electrical field stimulation (EFS) or pelvic nerve stimulation (PNS) caused inhibition of spontaneous contractions followed by off-contractions. Indomethacin (10-30 microM) caused concentration-dependent reductions in amplitude and duration of EFS- and PNS-evoked off-contractions but not latency. The NO synthase inhibitors, N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) (each at 100 microM) significantly reduced latency, amplitude, and duration of off-contractions evoked by EFS and PNS. This inhibition was partially reversed by L-arginine (120 microM) but not by D-arginine. Incubation of colonic strips with alpha-chymotrypsin (2 U/ml) decreased latency, amplitude, and duration of NANC off-contractions. L-NNA reduced amplitude, duration, and latency of off-contractions in preparations pretreated with alpha-chymotrypsin. Hydroquinone (10-30 microM), a generator of superoxide anions, caused significant depression of amplitude, duration, and latency of off-contractions which was completely reversed by superoxide dismutase (200 U/ml). These data suggest that the components of NANC off-contractions evoked by EFS and PNS involve peptides, NO, and prostaglandins.
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PMID:A nitric oxide and prostaglandin-dependent component of NANC off-contractions in cat colon. 750 99

Infarcted areas of rabbit myocardium show relatively higher inducible nitric oxide synthase activity, measured by the conversion of L-[14C]arginine to L-[14C]citrulline. The principal finding in this study is that dexamethasone (2 mg/kg) prevents the induction of inducible nitric oxide synthase in heart muscle when given before, or even 3 hr after coronary artery ligation. Additionally cyclic GMP levels remain unchanged following treatment with dexamethasone. It is possible that the enhanced production of nitric oxide by inducible nitric oxide synthase accounts, at least in part, for the depression of myocardial contractility seen in myocardial infarction and in other clinical conditions.
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PMID:Dexamethasone inhibits the expression of an inducible nitric oxide synthase in infarcted rabbit myocardium. 751 19

CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine (L-NNA) or N-nitro-L-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO.
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PMID:Cerebral blood flow changes during cortical spreading depression are not altered by inhibition of nitric oxide synthesis. 752 32

Enhanced production of nitric oxide has been implicated in cardiac and vascular dysfunction associated with septic and endotoxic shock. To test this hypothesis, conscious rats were administered endotoxin. 6 h later, the rats were anesthetized, arterial pressure was measured, and hearts were removed for Langendorff perfusion in the absence and presence of .01 microM isoproterenol. Left ventricular developed pressure was 61 +/- 6 mmHg in control rats 39 +/- 5 mmHg in endotoxin-treated rats. Inotropic responses to isoproterenol were unaffected by endotoxin treatment. Administration of nitric oxide synthase (NOS) inhibitors (NG-nitro-L-arginine and aminoguanidine) prior to endotoxin did not improve left ventricular function in endotoxin-treated rats. Dexamethasone pretreatment, however, prevented endotoxin-induced cardiac depression. These results suggest that cardiac depression during endotoxemia is not caused by NOS activation and increased nitric oxide production. Furthermore, the cardioprotectant actions of dexamethasone are not related to its ability to inhibit inducible NOS expression.
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PMID:Nitric oxide synthase inhibition does not prevent cardiac depression in endotoxic shock. 753 6

The cellular location of the NO-synthase involved in long-term depression (LTD) of parallel fiber (PF)-mediated EPSCs induced by raising the external potassium (K) concentration has been investigated by using both whole-cell patch-clamp recordings (WCR) of Purkinje cells (PCs) in thin slices in vitro, and reverse transcription followed by polymerase chain reaction (PCR) applied to mRNAs harvested from these single PCs during WCR. In all tested cells in the control group, a large LTD of PF-mediated EPSCs was induced by perfusing the slices for 3 min with a high (30 mM) K perfusing medium. In a second group of cells for which the protein kinase C (PKC) inhibitor peptide 19-36 was added to the intrapipette solution at a concentration of 10 microM, the LTD following complete wash out of the high K solution was significantly less prominent than in the control group. Very similar results were also obtained when 30 microM NG-methyl-L-arginine (L-NMMA) was added to the perfusing medium. In contrast, when both the PKC inhibitor peptide 19-36 and L-NMMA were added to the intrapipette solution at a concentration of 10 and 30 microM respectively, no LTD was revealed following wash out of the high K solution. Finally, the PCR amplification of mRNAs harvested from these single PCs during WCR, as well as from granule cells from the same slices, confirms that mRNAs encoding the NO-synthase are expressed by granule cells, whereas they are not detected in PCs.
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PMID:Cellular locus of the nitric oxide-synthase involved in cerebellar long-term depression induced by high external potassium concentration. 753 21

1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha. The protective action of L-NAME in the presence of cytokines was concentration-dependent and was not seen at a higher concentration (10 micro M) due to the significant reduction in coronary flow observed at this concentration.5. In contrast, when L-NAME (3 micro M) was given in the absence of IL-l beta plus TNF-alpha it depressed contractile function over the 2 h perfusion period by significantly reducing coronary flow.6. Inhibition of protein synthesis with cycloheximide (Cx) abolished the loss in function that occurred over 2h in both control and IL-1 beta plus TNF-a-treated hearts.7. Inducible, Ca2+-independent NO synthase activity was not observed in freshly isolated hearts but was observed in control hearts perfused for 2 h in vitro and was doubled in hearts perfused with IL-1 beta plus TNF-a. Cx prevented the expression of Ca2+-independent NO synthase in both control and cytokine-treated hearts.8. In summary, these results suggest that the depression of myocardial function by IL-l beta plus TNF-alpha is mediated, at least in part, by induction of Ca2+-independent NO synthase activity in the heart.
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PMID:The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. 753 96

Homosynaptic long-term depression (LTD) was studied in hippocampal slices from 12-18-d-old rats using field EPSP recording in the apical dendritic layer of CA1 pyramidal cells. Independent estimates of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N-methyl-D-aspartic acid (NMDA) receptor-mediated components of the field EPSP were obtained in parallel using early and late measurements of a dual-component EPSP in a low-magnesium solution. LTD was induced by low-frequency stimulation (LFS; 2 Hz for 10 min), resulting in equal relative changes of the AMPA and NMDA receptor-mediated components. Under conditions when the AMPA receptor-mediated component was fully blocked, a similarly sized LTD was observed for the pure NMDA receptor-mediated EPSP (measured as initial slope or peak amplitude). Equal changes in AMPA and NMDA receptor-mediated components occurred also upon application of the adenosine agonist N6-cyclohexyladenosine (CHA), known to act by decreasing transmitter release. On the other hand, LTD was found to interact in a multiplicative manner with the presynaptic release changes induced by CHA and by paired-pulse facilitation. The induction of the LTDs of both AMPA and NMDA receptor-mediated EPSPs was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid and by the phosphatase inhibitor okadaic acid. Partial blockade of LTD by okadaic acid resulted in equal partial blockade of the LTDs of the AMPA and NMDA receptor-mediated components. On the other hand, the L-type calcium channel blocker nifedipine, the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, the nitric oxide synthase inhibitor N omega-nitro-L-arginine, and the heme oxygenase inhibitor protoporphyrin IX zinc(II) had no effect on LTD of either the AMPA or the NMDA receptor-mediated component. These results of equal changes of AMPA and NMDA receptor-mediated components of the field EPSP in association with LTD, and the consistent parallelism of effects or noneffects on these components by various receptor antagonists and enzyme inhibitors, seem more easily explained by a presynaptic locus for LTD than by a postsynaptic one.
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PMID:On the linkage between AMPA and NMDA receptor-mediated EPSPs in homosynaptic long-term depression in the hippocampal CA1 region of young rats. 754 Jun 77

The decreased contraction amplitude of isolated cardiac myocytes from guinea pigs exposed to lipopolysaccharide (LPS) was reported to be partially reversed by nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) [Brady, et al., Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1963-H1966, 1992]. We have tested the potential involvement of NO formation in LPS-induced cardiac depression in the intact heart. Isolated perfused hearts of LPS-treated guinea pigs (4 mg/kg 4 h before organ removal) displayed a greatly decreased left ventricular pressure (LVP) when compared with untreated controls (48 +/- 11 vs. 93 +/- 18 mmHg, n = 6 hearts each), whereas heart rate and coronary flow were similar. Perfusion of LPS-treated hearts with L-NMMA or L-NAME (100 microM each) at constant flow did not increase LVP (50 +/- 14 and 44 +/- 11, respectively, vs. 52 +/- 14 mmHg). However, coronary resistance increased significantly. There was no difference between LPS-treated and control hearts in venous adenosine release (104 +/- 58 vs. 133 +/- 86 pmol.min-1.g-1). Measurement of the activities of the induced (iNOS) and constitutive forms of NOS revealed that there was no difference in total NOS activity (237 +/- 82 vs. 181 +/- 97 fmol.min-1.mg protein-1. There was no measurable induction of iNOS in the LPS-treated hearts either. Finally, cardiac energy status was studied by 31P nuclear magnetic resonance spectroscopy. There was no difference between LPS-treated and control hearts in myocardial ATP, creatine phosphate, pH, and free ADP (59 +/- 20 vs. 50 +/- 27 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide. 754 61

We examined whether blockade of prostaglandin synthesis by indomethacin could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the cerebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diameter, and NOS activity was determined by the conversion assay of [14C]arginine to [14C]citrulline. CSD dilated pial arterioles by 47 +/- 3% (baseline = 80-88 microns) (n = 21, P < 0.05), and inhibition of NOS by NG-nitro-L-arginine (L-NNA) (15 mg/kg iv) reduced dilation during CSD by over one-half (n = 8, P < 0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg iv), CSD dilated arterioles from 73 +/- 2 to 152 +/- 6 microns (n = 4, P < 0.05). However, after administration of both indomethacin and L-NNA (n = 5), CSD-induced arteriolar dilation was not different from the situation where indomethacin alone was given. Thus indomethacin completely abolished the inhibitory effect of L-NNA on CSD-induced dilation. Administration of L-NNA inhibited NOS activity in brain cortex almost completely (n = 8, P < 0.05), whereas indomethacin itself had no effect (n = 8). In addition, L-NNA inhibited topical acetylcholine (10(-5) M)-induced arteriolar dilation (n = 3, P < 0.05), and this effect was not altered by indomethacin (n = 4). In summary, L-NNA reduced arteriolar dilation during CSD. However, after administration of indomethacin, L-NNA does not reduce CSD-induced arteriolar dilation.
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PMID:Nitric oxide and prostaglandins interact to mediate arteriolar dilation during cortical spreading depression. 754 55


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