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

Inflammatory mediators released by macrophages (M phi) are believed to be involved in septic vasoplegia. To investigate the effect of M phi on vascular reactivity, excised rabbit carotids were exposed intraluminally either to peritoneal rabbit M phi, activated by 18 h of incubation with 1 microgram/ml lipopolysaccharide, or to the supernatants (SPN) derived from them. The contractile responses to phenylephrine (PE, 10(-6) M) were determined by measuring changes in diameter using an ultrasonic microdimensiometer 1, 2, and 3 h after the first control contraction. In control arteries (n = 12), PE-induced contractions were, respectively, 102.9 +/- 3.3%, 95.2 +/- 4.1%, and 89.7 +/- 3.8% of the first contraction, after 1, 2, and 3 h. Activated M phi significantly reduced PE-stimulated contractions after as little as 1 h of carotid exposure (percentage of controls at 1, 2, or 3 h: 74.1 +/- 5.6, 57.2 +/- 5.2, and 34.2 +/- 5.6, n = 10, P less than 0.001). The activated macrophage-derived SPN took longer to diminish carotid contractility than the M phi themselves, and became significant only after 2 h. The greater effect of M phi might be due to cooperation between M phi and vascular cells, as suggested by the amplified interleukin-1 release observed after M phi infusion. The presence of the endothelium partially protected carotid contractility from depression by activated M phi. Extraluminal addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis prevented this depression in arteries with or without endothelium. No products of the oxidative pathway of L-arginine were detected in rabbit activated M phi. These results suggest that activation of this pathway in smooth muscle cells seems to be involved in vascular hypocontractility.
 ...
PMID:Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release. 154 77

Reports on neuropsychological assessment and psychopathological symptoms in HIV-1 patients are rather different. The aim of the study was to assess frequency and extent of noopsychic changes and psychopathological symptoms in HIV-1 patients of different risk groups. Of the 77 patients being included in the study 35 patients belonged to risk group 1, 42 to risk group 2. The patient groups were compared to a control-group of healthy volunteers (n = 50) and to a control-group of HIV-negative i.v. drug-addicts (n = 31). The psychometric test battery included Raven and MWT Test, Benton Test, numerical memory Test, ARG Test. Personality variables were assessed by MMPI, Psychopathology by AMDP-System, Hamilton Depression Scale, Wellbeing Scale (von Zerssen), STAI 1 and 2 and BPRS. Patients of risk group 1 showed significantly less impairment of noopsychic performance than patients of risk group 2. Risk group 1 showed only in the Benton Test significant impairment compared to healthy volunteers while risk group 2 in most of the tests was impaired. Risk group 2 did not show impairment compared to the control-group of seronegative drug users. Depressive syndromes mainly in risk group 2 showed a significant influence on the noopsychic performance.
 ...
PMID:[Noopsychological changes and psychopathological characteristics of HIV-1 patients of various risk groups]. 154 16

The tone of vascular smooth muscle is influenced by factors released from the endothelium, including endothelin (ET)-1 and endothelium-derived relaxing factor (EDRF). To better understand the interactions between these two mediators, we examined the release of both immunoreactive ET-1 (ir-ET-1) and EDRF from bovine aortic intact endothelium. Bovine aortas were opened longitudinally, washed, and clamped with the endothelium uppermost between two plates. The upper plate contained six openings forming identical and independent wells of endothelial cell monolayer. In experiments examining the release of EDRF, measured as accumulated NO2- and NO3- (NO chi -), we found that ET-3, calcium ionophore A23187 (A23187), acetylcholine (ACh), or ADP caused significant increase in NO chi- release, whereas ET-1 did not. These were significantly reduced in the presence of the EDRF/NO synthase inhibitor, NG-methyl-L-arginine (L-NMA). In a parallel series of experiments measuring EDRF release by stimulation of guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rat fetal lung (RFL)-6 cells, ET-3 but not ET-1 was also found to be active as a releaser of EDRF. A23187 caused an increase of ir-ET-1 release, whereas ACh, ADP, or the NO-containing compound sodium nitroprusside decreased the release of ir-ET-1. The depression in ir-ET-1 release in the presence of ACh or ADP was not seen when the endothelium was treated with L-NMA. When the cells were pretreated with 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), the release of ir-ET-1 in response to A23187 was significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interactions of endothelins and EDRF in bovine native endothelial cells: selective effects of endothelin-3. 159 Apr 65

1. Isolated rings of rabbit external jugular vein (RbJV) and rat thoracic aorta (RA) were used to study the effect of the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) on muscarinic and 5-hydroxytryptamine (5-HT) receptor-stimulated, endothelium-dependent vascular relaxations. 2. In RbJV relaxations produced by the endothelial 5-HT receptor agonist alpha-methyl-5-HT were potently and non-surmountably inhibited by L-NAME (10 microM), whereas acetylcholine relaxations in this tissue were unaffected by this concentration of inhibitor. By contrast, acetylcholine relaxations in RA were virtually abolished by 10 microM L-NAME. In each case an equivalent concentration of D-NAME was without effect on agonist-induced relaxations. 3. The different effect of L-NAME on acetylcholine relaxations in RbJV and RA was not due to muscarinic receptor differences. Affinity estimates for acetylcholine (pKA = 6.12 +/- 0.09; 6.09 +/- 0.08 respectively) and for 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP, pKB = 9.01 +2- 0.012; 9.24 +/- 0.16 respectively) indicated that the receptors in both tissues belong to the same M3 class. Tissue differences resulting from the release of a cyclo-oxygenase product or a glibenclamide-sensitive K(+)-channel-linked hyperpolarizing factor were also ruled out by selective inhibition of these pathways. 4. When phenoxybenzamine was used to reduce the efficacy of acetylcholine in RbJV so that it behaved as a partial agonist in this tissue, L-NAME (10 microM) now produced non-surmountable inhibition of relaxation responses. In untreated tissues the same concentration of L-NAME also profoundly inhibited responses produced by butyrylcholine and pilocarpine, both of which behave as partial agonists at the M3 receptor in RbJV. 5. A simple model was developed which describes the theoretical behaviour of receptor-stimulated synthesis and release of NO. The model predicts that competitive inhibition of NO formation results in parallel displacements of the agonist response curve in the case of high efficacy agonist, but right-shift with concomitant depression of the curve maximum in the case of low efficacy agonists. Simulations based on the model showed reasonable agreement with the experimental data. 6. It is concluded that analogues of L-arginine demonstrate tissue- and agonist-dependence in terms of their ability to inhibit receptor-mediated events involving the liberation of NO. This behaviour can reflect differences in agonist efficacy in the receptor systems being studied, a possibility that should be ruled out before apparent resistance to inhibition is taken as evidence for the involvement of heterogeneous endothelium-derived relaxing factors (EDRFs).
 ...
PMID:Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence. 162 52

1. The effects of bradykinin (BK) in the microcirculation of the isolated perfused heart of the rat were examined. The kinin receptors mediating the effects of BK were characterized and the role of endothelium-derived relaxation factor (EDRF) and prostacyclin investigated. 2. The dose-related vasodilator responses elicited by bolus doses of BK (0.001-10.0 nmol) were competitively blocked by the selective kinin B2 receptor antagonist [D-Arg0,Hyp3, Thi5.8,D-Phe7]-bradykinin (pA2 = 6.8). Des-Arg9-bradykinin, a selective kinin B1 receptor agonist had no vasodilator activity at doses of up to 10 nmol. 3. L-NG-nitro arginine (100 microM; L-NOArg), an inhibitor of endothelium-dependent vasodilatation, reduced the duration but not the magnitude of the BK vasodilator response. This action of L-NOArg was not reversed by L-arginine (100 microM). 4. Superoxide dismutase (10 units ml-1), haemoglobin (10 microM) and methylene blue (MB; 1 microM), all known to modify EDRF-mediated responses, failed to alter the vasodilator action of BK. 5. Gossypol (1-15 microM), a presumed inhibitor of EDRF biosynthesis, caused a marked drop in perfusion pressure followed by vasoconstriction. These changes in coronary tone were accompanied by an irreversible depression of cardiac contractility and heart rate. Over the same concentration range gossypol abolished the vasodilator action of BK (1.0 nmol), however it also blocked the endothelium-independent vasodilator response to sodium nitroprusside (30 nmol) and the vasoconstrictor effect of endothelin-1 (10 pmol) which suggests non-specific toxic actions of gossypol. 6. Bolus injections of BK (0.001-1.Onmol) failed to elevate basal levels of prostacyclin (PGI2) as shown by assaying for its stable metabolite 6-keto-PGF<,,. In addition, BK-induced vasodilatation was not blocked by flurbiprofen (2 microM) or BW755C (7.5 microM) which are inhibitors of the arachidonic acid pathway. When added with L-NOArg (100 microM), flurbiprofe(10 microM) did not potentiate the inhibitory action of L-NOArg on the BK response. 7. These results show that the vasodilator action of BK in the rat heart is dependent on the activation of the kinin B2 receptors but independent of PGI2 release. Although a conclusive role for EDRF could not be established, this study has questioned the suitability of several agents commonly used as inhibitors of EDRF-mediated responses.
 ...
PMID:Effects of bradykinin in the rat isolated perfused heart: role of kinin receptors and endothelium-derived relaxing factor. 165 68

1. The aim of this investigation was to study the relationship between contractile responsiveness, activation of the L-arginine pathway and tissue levels of guanosine 3':5'cyclic monophosphate (cylic GMP) in aortic rings removed from rats 4 h after intraperitoneal administration of bacterial endotoxin (E. coli. lipopolysaccharide, LPS, 20 mg kg-1). 2. LPS-treatment resulted in a reduction of the sensitivity and maximal contractile response to noradrenaline (NA). 3. Depression of the maximal contractile response was restored to control by 6-anilo-5,8-quinolinedione (LY 83583, 10 microM), which prevents activation of soluble guanylate cyclase. 4. Cyclic GMP levels in tissue from LPS-treated rats were 2 fold greater than cyclic GMP levels detected in tissue from control (saline-treated) rats. The LPS-induced increase in cyclic GMP content was observed both in the presence and absence of functional endothelium. 5. Addition of L-arginine 1 mM) to maximally contracted aortic rings produced significantly relaxation of rings from LPS-treated rats but not rings from control animals. In the LPS-treated group, addition of L-arginine was also associated with a significant increase in cyclic GMP content. L-Arginine had no effect on the cyclic GMP content of control rings. D-Arginine (1 mM) was without effect. 6. In rings from LPS-treated rats, NG-nitro-L-arginine methyl ester (L-NAME, 300 microM), an inhibitor of nitric oxide (NO) production, increased the contractile response to NA and prevented the LPS-induced increase in cyclic GMP content. In control rings, L-NAME increased the NA sensitivity only when the endothelium remained intact and reduced the cyclic GMP content of these rings to that of control endothelium-denuded rings. 7. These results demonstrate that LPS-induced hyporeactivity to NA occurs secondarily to activation of the L-arginine pathway and subsequent activation of soluble guanylate cyclase in vascular tissue. In addition they suggest that LPS induces the production of an NO-like relaxing factor in non-endothelial cells.
 ...
PMID:Evidence that an L-arginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. 167 81

Conjunctive stimulation of climbing and parallel fibres in the cerebellum evokes a long-term depression of parallel-fibre Purkinje-cell transmission, a phenomenon implicated as the cellular mechanism for cerebellar motor learning. It is suspected that the increase in cyclic GMP concentration that occurs after activation of climbing fibres is required to evoke long-term depression. Excitatory amino acids are known to cause the release of nitric oxide (NO), resulting in elevation of the cGMP level in the cerebellum. Here we report that endogenous NO is released after stimulation of climbing fibres, that long-term depression evoked by conjunctive stimulation of parallel and climbing fibres is blocked by haemoglobin (which strongly binds NO) or L-NG-monomethyl-arginine (an inhibitor of NO synthase), and that exogenous NO or cGMP can substitute for the stimulation of climbing fibres to cause long-term depression in rat cerebellar slices. These results demonstrate that the release of endogenous NO is essential for the induction of synaptic plasticity in the cerebellum.
 ...
PMID:Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. 170 79

Interleukin-1 beta (IL-1) reduces vascular smooth muscle contractility. The purpose of the present study was to investigate the role of nitric oxide synthesis in mediating this effect of IL-1. We studied the influence of inhibitors of nitric oxide synthesis on the depression of norepinephrine-induced contractions of rat aortic rings by IL-1. Also, we examined the ability of IL-1 to increase the production of nitric oxide by rat aortic smooth muscle cells in culture as determined indirectly by measuring nitrite concentrations. NG-amino-L-arginine blocked the effect of IL-1 on norepinephrine-induced contractions of rat aortic rings whereas NG-monomethyl-L-arginine and NG-nitro-L-arginine were considerably less effective. In addition, this effect of IL-1 was prevented by coincubation of the rings with cycloheximide. IL-1 greatly elevated nitrite production by rat aortic smooth muscle cells, and this effect could also be blocked completely by the arginine analogs. NG-amino-L-arginine was the most potent inhibitor of nitrite synthesis (IC50 = 1.7 microM) whereas NG-monomethyl-L-arginine and NG-nitro-L-arginine were about 10-fold less potent (IC50 = 16 and 22 microM, respectively). These results suggest that IL-1-induced depression of norepinephrine-induced vascular contraction is mediated by the increased synthesis of nitric oxide synthase by vascular smooth muscle cells. The relative potency of the arginine analogs for the inhibition of nitrite synthesis suggests that the synthase in vascular smooth muscle is similar to the synthase in macrophages.
 ...
PMID:Nitric oxide synthase inhibitors inhibit interleukin-1 beta-induced depression of vascular smooth muscle. 171 80

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.
 ...
PMID:Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators. 172 Aug 43

Studies indicate that simple hemorrhage produces a profound depression of cell-mediated immunity, thereby contributing to an enhanced susceptibility to septic challenge in the host. However, it remains unknown whether or not the macrophages' cytotoxic capacity is altered after hemorrhage. To study this, C3H/HeN mice were bled to and maintained at a blood pressure of 35 mm Hg for 60 min, and adequately resuscitated. Mice were then killed at 2 or 24 h after hemorrhage to obtain peritoneal macrophage, splenic macrophage, and Kupffer cells. Cytotoxicity was assessed by determining the capacity of these macrophages to lyse [3H]TdR labeled WEHI-164 clone 13 or P815 tumor target cells (WEHI-164, sensitive to both soluble and cell-associated TNF vs P815 cells, insensitive to soluble TNF). Peritoneal and splenic macrophages from hemorrhaged animals exhibited a significantly reduced cytotoxic capacity, whereas Kupffer cells' ability to kill the target cells was enhanced. Similarly, the Kupffer cells' capacity to release TNF and IL-1, as well as express cell-associated forms of this cytokine are significantly enhanced on macrophages isolated 2 h after hemorrhage, whereas peritoneal macrophages are not. Furthermore, antibodies directed at mouse TNF but not against murine IL-1 alpha or murine IL-6 were able to oblate the enhanced target cell lysis of unfixed, as well as paraformaldehyde fixed (metabolically inactive) Kupffer cells. Studies using inhibitors (GN-monomethyl-arginine, superoxide dismutase, catalase, and ibuprofen) of other TNF-inducible mechanisms of target cell killing indicated that only the inhibition of the release of reactive nitrogen consistently depressed the cytotoxic capacity of Kupffer cells from hemorrhaged mice. Thus, the increased Kupffer cell cytotoxicity from hemorrhaged mice is most likely mediated through the expression of cell-associated TNF and the release of reactive nitrogen.
 ...
PMID:Hemorrhage induces enhanced Kupffer cell cytotoxicity while decreasing peritoneal or splenic macrophage capacity. Involvement of cell-associated tumor necrosis factor and reactive nitrogen. 175 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>