Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of N omega-nitro-L-arginine methyl ester (L-NAME) i.v. and nitric oxide (NO) inhalation on integrated systemic responses to cocaine were studied in lightly anesthetized, paralyzed, and mechanically ventilated rats. Cocaine (4 mg/kg/min i.v.) produced seizures then isoelectric electrocephalographic (isoEEG) activity as well as an initial increase in systolic blood pressure and heart rate, then progressive cardiovascular system depression culminating in asystole. Pretreatment with L-NAME (2 mg/kg/min i.v.) for 30 min significantly reduced the incidence of seizure as compared to saline treated animals (saline 7/8; L-NAME 3/8). Doses of cocaine that produced arrhythmias, isoEEG and asystole were significantly lower in the L-NAME treated animals as compared to the saline group. L-NAME did not affect peak systolic blood pressure and heart rate responses to cocaine. No inhalation (80 ppm) did not affect CNS and cardiovascular responses to cocaine in control animals but enhanced the effects of L-NAME on cocaine toxicity. The results show that pretreatment with L-NAME reduces the central nervous system stimulatory effect of cocaine (reduced seizure incidence) and enhances its depressant effect on both the central nervous system (lower does for isoEEG) and the cardiovascular system (lower dose for arrhythmias and asystole), but does not affect the cardiovascular stimulatory action of cocaine. NO inhalation does not protect against any of the systemic effects of cocaine in animals with normal or suppressed NO production.
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PMID:Effects of nitric oxide synthesis inhibition with or without nitric oxide inhalation on responses to systemic cocaine administration in rats. 754 46

Probable participation of two second messengers, NO and cGMP, in short- and long-latent effects of 15(S)-hydroxy-(5Z,8Z,11Z, 13E)-eicosatetraenoic acid (15-HETE, acyclic eicosanoid) on plasticity of somatic acetylcholine receptors on identified neurons of Helix lucorum was studied using two-electrode voltage clamp technique. It was shown that inhibitor of NO synthase N omega-Methyl-L-Arginine and inhibitors of soluble guanylate cyclase LY-83,583 and methylene blue disturbed short- and long-latent modulatory effects of 15-HETE on depression depth of the inward current evoked by rhythmic acetylcholine application on the neuron soma. We suppose that NO and cGMP participate in short- and long-latent effects of 15-HETE on plasticity of acetylcholine receptors.
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PMID:[Inhibitors of NO-synthase and guanylate cyclase block the modulation of cholinoreceptor plasticity in snail neurons by 15-hydroxyeicosatetraenoic acid]. 754 53

Nerve cells release nitric oxide (NO) in response to activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We explored the hypothesis that NO influences the changes of cerebral blood flow (CBF) during cortical spreading depression (CSD), which is known to be associated with NMDA receptor activation. CBF was monitored in parietal cortex by laser-Doppler flowmetry in halothane-anesthetized rats. Under control conditions, CSD induced regular changes of CBF, which consisted of four phases: a brief hypoperfusion before the direct current (DC) shift; a marked CBF rise during the DC shift; followed by a smaller, but protracted increase of CBF; and a prolonged CBF reduction (the oligemia). NO synthase inhibition by intravenous and/or topical application of NG-nitro-L-arginine enhanced the brief initial hypoperfusion, but the CBF increases and the oligemia were unchanged. L-Arginine prevented the development of the prolonged oligemia after CSD but had no influence on the marked rise of CBF during CSD. Animals treated with L-arginine recovered the reduced vascular reactivity to hypercapnia after CSD much faster than control rats. Functional denervation of cortical and pial arterioles by tetrodotoxin accentuated the pre-CSD hypoperfusion and the oligemia but did not affect the CBF increases. The results suggest that NO is important for the changes of cerebrovascular regulation following CSD. The observations may have clinical importance, since CBF changes during migraine may be triggered by CSD.
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PMID:Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression. 763 52

Chronic heart failure (CHF) impairs endothelium-dependent vasodilatation of large conductance arteries. We investigated whether a similar reduction also occurs in small arteries, and whether such a reduction can be prevented by the angiotensin converting enzyme inhibitor perindopril (P) in a rat model of CHF (left coronary artery ligation). After 1 month treatment with placebo or P (2 mg/kg/day), rats were anesthetized and arterial pressure, left ventricular end-diastolic pressure, and central venous pressure were measured with a micromanometer. Segments of aorta and mesenteric artery (mean diameter, 281 +/- 8 microns) were then isolated, cannulated, and perfused at constant pressure using an arteriograph. Responses to increasing concentrations of acetylcholine (Ach), nitroprusside, and to 10(-4) mol/L NG-nitro-L-arginine methyl ester (L-NAME) were studied after preconstriction by phenylephrine. Heart failure resulted in a decrease in systolic and diastolic pressures, an increase in left ventricular end-diastolic and central venous pressures, and a significant depression of Ach-induced dilatation of the mesenteric artery (maximal dilatation, from 90 +/- 4% to 63 +/- 4%, P < .05) but not of the aorta (from 56 +/- 8% to 45 +/- 5%, NS) without any modification in the endothelium-independent vasodilatation induced by nitroprusside. In the group treated by the angiotensin converting enzyme (ACE) inhibitor perindopril, systolic and diastolic pressures were slightly decreased, whereas left ventricular end diastolic, central venous pressures, and the endothelium-dependent vasodilating response to Ach were normalized. Responses to L-NAME were not affected by CHF or perindopril. Perindopril also decreased hypertrophy, as evidenced by a significantly lower heart weight in treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of endothelial dysfunction in small and large arteries in a model of chronic heart failure. Effect of angiotensin converting enzyme inhibition. 764 44

The immune system of the spontaneously hypertensive rat is dysfunctional compared with that of normotensive control strains. Previous studies from our laboratory have shown that immunodepression in the spontaneously hypertensive rat was mediated by macrophages. The current study examines the mechanism for the depressed proliferative responses to concanavalin A typically observed by splenic mononuclear cells of spontaneously hypertensive rats. We tested various inhibitors of known macrophage products responsible for suppressing lymphoid function. The nitric oxide synthetase inhibitor NG-monomethyl L-arginine produced dose-dependent derepression of the proliferative responses of splenic mononuclear cells to concanavalin A. In contrast, indomethacin and catalase exhibited only weak derepression of the proliferative responses. Subsequent analysis showed that splenic mononuclear cells from spontaneously hypertensive rats generated greater nitric oxide levels than cells from Wistar-Kyoto rats, and nitric oxide levels were reduced when the inhibitor was added to splenic mononuclear cell cultures from spontaneously hypertensive rats. We further demonstrated that L-arginine is required for the development of the depressed mitogen-induced proliferative responses in these cells. Addition of L-arginine in excess of 10 microM to cultures diminished cell proliferation and increased nitric oxide. Polyclonal antibodies to murine interferon gamma reduced nitric oxide accumulation by approximately 50%, suggesting that interferon gamma is partially responsible for enhancing nitric oxide production in mitogen-stimulated splenic mononuclear cell cultures from spontaneously hypertensive rats. Thus, this study provides evidence that the immune depression observed in the spontaneously hypertensive rat is nitric oxide dependent.
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PMID:Nitric oxide mediates immune dysfunction in the spontaneously hypertensive rat. 767 89

1. The effects of NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), their D-isomers, and dexamethasone on noradrenaline (NA)-induced contractions and antagonism by alpha-adrenoceptor antagonists, have been investigated in rat isolated thoracic aortic rings with/without endothelium. 2. NA produced concentration-dependent contractions of isolated aortic rings with EC50 values of 2.41 +/- 0.54 (n = 21) and 28.00 +/- 8.50 (n = 25) nM for endothelium-denuded and -intact preparations respectively. Acetylcholine (ACh) relaxed NA-precontracted rings with intact, but not those denuded of endothelium. 3. Treatment with L-NAME (1-30 microM), or L-NMMA (10-500 microM), but not their D-isomers, resulted in an endothelium-dependent enhancement of NA-induced contractions. Pre-treatment, in vitro, with 0.5 microM dexamethasone neither directly potentiated, nor influenced L-NAME-induced potentiation of NA-mediated contractions in endothelium-intact rings; however, dexamethasone pretreatment reduced EC50 values for NA, and also prevented L-NAME-induced potentiation, in denuded rings equilibrated for 5 h under resting tension. 4. In both intact and denuded rings, phentolamine, prazosin and WB 4101 shifted NA concentration-response curves to the right; L-NAME, and also L-NMMA, but not their D-isomers, reversed the blockade as indicated by significant decreases in NA dose-ratios. In denuded rings, reversal by L-NAME or L-NMMA was prevented following pretreatment with dexamethasone. 5. Following treatment with 5 or 50 nM phenoxybenzamine (PBZ), NA concentration-response (C-R)curves were shifted to the right with marked depression of maximal responses; 100 microM L-NAME reversed the antagonism in both endothelium intact and denuded rings. However, 500 nM PBZ treatment resulted in complete abolition of the responses to NA, and contractions were not restored by either L-NAME or L-NMMA.6. 5-Hydroxytryptamine (5-HT)-induced contractions of aortic rings were potentiated by endothelium denudation and also by L-, but not D-, NAME. 5-HT-induced contractions were non-competitively antagonized by 10nM ritanserin, and 100 microM L-NAME partially reversed the antagonism in intact but not denuded rings.7. It is concluded that the inhibition of constitutive endothelial NO synthase and inducible smooth muscle NO synthase accounts for the ability of L-NAME, and L-NMMA, to potentiate the effects of agonists and reduce alpha-adrenoceptor antagonism in endothelium-intact and denuded rings. Furthermore,endothelial cell removal/damage triggers the induction of a smooth muscle NO synthase.
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PMID:Interactions of nitric oxide synthase inhibitors and dexamethasone with alpha-adrenoceptor-mediated responses in rat aorta. 768 95

The effects of dexamethasone (DEX) were studied on early and delayed hyporesponsiveness to noradrenaline (NA) induced by Escherichia coli lipopolysaccharide (LPS) in pentobarbitone-anesthetized rats, and in aortic rings, which were either removed from LPS-treated rats or exposed to LPS in vitro. In all three preparations, the LPS-impaired responses to NA were restored by N omega-nitro-L-arginine methyl ester. In addition, delayed depression of NA-induced aortic contractions was enhanced by L-arginine (1 mM). In control conditions, DEX had no effect on responses to NA. When administered before LPS, or before hyporeactivity was fully developed, DEX (5-10 mg/kg or 10 microM) entirely prevented both the early decline in responses to NA or its progression, and the delayed impaired aortic contraction induced by LPS. However, DEX did not prevent the transient drop in mean arterial blood pressure (which was maximal at 20 min after the onset of LPS infusion) observed before the full development of impaired reactivity to NA (reached after 55 min). Neither did DEX modify the responses to NA, in vivo or in vitro, once LPS-induced hyporesponsiveness was fully established. These results indicate that DEX inhibits both the onset of impaired responsiveness to NA, which probably involves the early stimulation of the constitutive nitric oxide (NO) synthase, and persistent vascular hyporeactivity resulting from the delayed induction of NO-synthase by LPS. In addition, they show that DEX has no effect on hyporeactivity to NA once fully established.
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PMID:Effect of dexamethasone on the onset and persistence of vascular hyporeactivity induced by E. coli lipopolysaccharide in rats. 769 12

Since arginine vasotocin (AVT) effects are mediated by serotonin, which was involved in the production of eating disorders, disorders which show many common mechanisms with the depressive disorders, and since AVT was used as treatment of depressive disorders, we investigated the AVT effects in a double-blind study with patients with eating disorders. We compared AVT effects on 15 patients with eating disorders to 18 patients with eating disorders which received tricyclic antidepressants or cognitive-behavioral psychotherapy. The severity of depression was assessed by means of the Hamilton Depression Scale and of Beck's Depression Inventory, before and after three months therapy. Data showed a significant improvement of depressive symptomatology after AVT treatment. Comparison of AVT effects on depression of eating disorders subgroups versus tricyclic antidepressant or psychotherapy treatment are discussed.
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PMID:Vasotocin effects in depressive patients with eating disorders. 769 65

Nocturnal asthma represents a unique subset of patients with asthma who experience worsening symptoms and airflow obstruction at night. The basis for this phenotype of asthma is not known, but beta 2-adrenergic receptors (beta 2AR) are known to downregulate overnight in nocturnal asthmatics but not normal subjects or nonnocturnal asthmatics. We have recently delineated three polymorphic loci within the coding block of the beta 2AR which alter amino acids at positions 16, 27, and 164 and impart specific biochemical and pharmacologic phenotypes to the receptor. In site-directed mutagenesis/recombinant expression studies we have found that glycine at position 16 (Gly16) imparts an accelerated agonist-promoted downregulation of beta 2AR as compared to arginine at this position (Arg16). We hypothesized that Gly16 might be overrepresented in nocturnal asthmatics and thus determined the beta 2AR genotypes of two well-defined asthmatic cohorts: 23 nocturnal asthmatics with 34 +/- 2% nocturnal depression of peak expiratory flow rates, and 22 nonnocturnal asthmatics with virtually no such depression (2.3 +/- 0.8%). The frequency of the Gly16 allele was 80.4% in the nocturnal group as compared to 52.2% in the nonnocturnal group, while the Arg16 allele was present in 19.6 and 47.8%, respectively. This overrepresentation of the Gly16 allele in nocturnal asthma was significant at P = 0.007 with an odds ratio of having nocturnal asthma and the Gly16 polymorphism being 3.8. Comparisons of the two cohorts as to homozygosity for Gly16, homozygosity for Arg16, or heterozygosity were also consistent with segregation of Gly16 with nocturnal asthma. There was no difference in the frequency of polymorphisms at loci 27 (Gln27 or Glu27) and 164 (Thr164 or Ile164) between the two groups. Thus the Gly16 polymorphism of the beta 2AR, which imparts an enhanced downregulation of receptor number, is overrepresented in nocturnal asthma and appears to be an important genetic factor in the expression of this asthmatic phenotype.
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PMID:Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. 770 71

In patch-clamped Purkinje cells (PCs), bath application of the ionotropic glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevents induction of long-term depression (LTD) of parallel fibre (PF)-mediated EPSPs by a pairing protocol between Ca2+ spike firing and PF stimulation whereas bath application of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate (mGLU) receptor antagonist, does not. On the other hand, LTD can be also induced by pairing direct depolarization of PCs with activation of mGLU receptors by 1S,3R-aminocyclopentyl-dicarboxylate (1S,3R-ACPD), even in the presence of CNQX. In this case, LTD induction is not consistently blocked by bath application of the nitric oxide synthase inhibitor, NG-methyl-L-arginine (L-NMMA), whereas it is strongly blocked when the protein kinase C inhibitor peptide 19-36 is dialysed into PCs. These results are at variance with LTD induced by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs which depends to the same extent on both cascades. Finally, thapsigargin, which depletes most intracellular Ca2+ pools, does not block induction of LTD by a pairing protocol between Ca2+ spikes and PF-mediated EPSPs whereas it prevents the induction of LTD depending on strong mGLU receptor activation.
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PMID:Receptors and second messengers involved in long-term depression in rat cerebellar slices in vitro: a reappraisal. 771 36


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