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

To clarify the mechanisms by which volatile anesthetics may depress myocardial contractility, the depressant effects of equivalent concentrations of isoflurane, enflurane and halothane were compared in rat and frog ventricular myocardium, preparations which differ markedly in excitation-contraction coupling. In Tyrode solution, right ventricular papillary muscles from rat exhibited very large, rapidly developing contractions after rest, with a subsequent negative force-frequency relation as the stimulation rate was increased to 0.1, 0.25, 0.5, 1, 2, and 3 Hz. The large contractions after rest and at 0.1 Hz were depressed by 0.75% halothane and 1.7% enflurane to about 60% of control, but less so by 1.3% isoflurane (approximately 0.8 MAC). Halothane at 1.5% was more depressant than 2.5% isoflurane at all stimulation rates, while 3.5% enflurane caused intermediate depression (approximately 1.6 MAC). Contractions in frog ventricular strips were studied in Ringer solution following rest and at stimulation rates of 0.1, 0.25, 0.5, and 1 Hz, in the absence and presence of equivalent anesthetic concentrations. At 0.1 to 1 Hz, isoflurane was less depressant than equivalent concentrations of halothane. Enflurane (1.7%) was less depressant than 0.75% halothane at 0.1 and 0.25 Hz; 3.5% enflurane was more depressant than 2.5% isoflurane at 1 Hz. Anesthetic effects on sustained contractures were also studied in frog ventricular strips that were superfused for 4-5 min with 40, 60, 80, and 100 mM K Ringer solution. Contractures induced by 80 and 100 mM K solution were depressed more by halothane (to 60% of control) than by isoflurane or enflurane (approximately 85% of control). However, only enflurane depressed the contractions at 1 Hz more than the sustained contractures in 100 mM K Ringer. The Ca2+ for activating contractions in rat ventricle is derived largely from the sarcoplasmic reticulum, the intracellular Ca2+ accumulation and release organelle. In contrast, Ca2+ for activating contractions in the frog ventricle originates primarily from the external medium. These results suggest that halothane is more potent than isoflurane in reducing the amount of Ca2+ rapidly released from the sarcoplasmic reticulum (as observed in rat), as well as in depressing entry of extracellular Ca2+ to activate myofibrils (as in frog). Enflurane appears to have intermediate potency with actions distinct from halothane and isoflurane. The greater potency of halothane may also be due in part to greater direct depression of actin-myosin ATPase.
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PMID:Depressant effects of volatile anesthetics upon rat and amphibian ventricular myocardium: insights into anesthetic mechanisms of action. 278 93

Metaphit, which acylates phencyclidine (PCP) receptors in vitro, was shown to acylate PCP receptors and antagonize the behavioral and electrophysiological effects of PCP in vivo. Metaphit (2 mumol/rat) administered i.c.v. produced PCP-like stereotyped behavior and ataxia in 10 to 20% of rats. At a lower dose, Metaphit (1 mumol/rat) antagonized the ability of PCP to induce stereotyped behavior and ataxia for 3 and 4 days, respectively. The Metaphit-induced antagonism of PCP induction of stereotyped behavior and ataxia was dose-dependent and specific as Metaphit did not antagonize induction of stereotyped behavior by amphetamine. Further evidence for a specific PCP receptor mechanism was the finding that PCP pretreatment blocked the effects of subsequent Metaphit administration. Metaphit also antagonized PCP-induction of stereotyped behavior, but not ataxia, after i.v. administration. Doses of Metaphit that produced long-term antagonism of the behavioral effects of PCP also produced a significant decrease in the maximum binding, but not Kd, of the binding of the PCP analog, [3H]-1-(2-thienyl)cyclohexyl]piperidine, in Metaphit-pretreated rats. The binding of [3H]etorphine and [3H]spiroperidol was not altered significantly by pretreating rats with Metaphit. (-)-Cyclazocine and (+)-SKF 10,047 induced stereotyped behavior and ataxia that was not antagonized by Metaphit-pretreatment. In electrophysiological experiments, Metaphit, like PCP, initially depressed the firing of caudate neurons as does PCP, but then irreversibly inhibited PCP-induced depression of caudate neurons. These results suggest that metaphit antagonized the effects of PCP by selectively acylating PCP receptors and that (-)-cyclazocine- and (+)-SKF 10,047-induced behavioral effects are not mediated primarily by PCP receptors.
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PMID:Metaphit, an acylating ligand for phencyclidine receptors: characterization of in vivo actions in the rat. 301 19

The purpose of the present study was to examine the pial arteriolar diameter and evoked vascular responses after single episodes of cortical spreading depression (CSD) in rats and cats in order to elucidate the mechanisms of the persistent change of cortical perfusion which succeeds CSD. This problem is of potential clinical interest also since CSD may be involved in migraine pathophysiology. Using an open cranial window technique, pial arteriolar diameters were measured with an image splitting method. Vascular reactivity was tested by local perivascular microapplication of mock cerebrospinal fluid (CSF) containing high and low levels of K+, high and low pH, adenosine and bradykinin before and after CSD which was triggered by intracortical injection of KCl. During CSD a monophasic vasodilatation of 26.0 +/- 3.7% (mean +/- S.E.M.; cat) or 64.6 +/- 3.9% (rat) was observed. Following CSD, the cat developed persistent vasodilatation (16.7 +/- 1.9%) while the rat exhibited vasoconstriction (12.1 +/- 1.8%). Both species displayed a severely impaired responsiveness to constrictor and dilating stimuli as compared to pre-CSD values. The responses were reduced by 28-84%, dependent on the substance tested. It is concluded that vascular reactivity is severely impaired after CSD (15-75 min) and that this might explain the impaired coupling between flow and metabolism after CSD.
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PMID:Change of cerebrovascular reactivity after cortical spreading depression in cats and rats. 360 27

Reticuloendothelial (RE) phagocytic function and plasma fibronectin are altered early after trauma and during septic shock. Since fibronectin-coated particles will tend to aggregate if not efficiently phagocytized, we hypothesized that elevated fibronectin levels during hepatic and/or splenic RE depression could potentiate the lung deposition of blood-borne foreign microparticles. To evaluate this concept, we measured plasma fibronectin, hepatic RE function, and tissue deposition of blood-borne colloids in rats after they were injected with nonbacterial and bacterial particulates. Rats were injected intravenously with gelatin-coated colloids (50 mg/100 gm) to simulate blood-borne collagenous tissue debris after trauma, or with live Pseudomonas aeruginosa (1 X 10(9)/rat) to simulate bacterial entrance into the blood with sepsis, or with both to simulate sepsis after trauma. Phagocytic function was evaluated by liver and spleen uptake of gelatinized 125I RE test emulsion. Fibronectin was quantified by electroimmunoassay. There was an acute 60-80% decrease in plasma fibronectin 2 hr following either colloid or colloid coupled with bacterial infusion. Bacterial infusion alone elicited only a mild 20% decrease in fibronectin by 2 hr. By 24 hr, restoration of fibronectin levels was observed in all groups with hyperfibronectinemia observed in animals challenged with Pseudomonas. Following colloid alone, liver uptake of the RE test particle was acutely depressed at 2 hr in association with an acute depletion of fibronectin, but at 24 hr the RE depression persisted even with normalization of fibronectin. In contrast, with only bacteremia, the rebound elevation of fibronectin was associated with increased hepatic RE function. In rats given both colloid and Pseudomonas, the hyperfibronectinemia (60-100% above controls) at 24 hr coexisted with inadequate liver phagocytic uptake ability. This resulted in a significant 20-fold (P less than 0.05) increment in lung localization of the blood-borne test microparticles. Thus, hyperfibronectinemia without a parallel increase in liver phagocytic ingestive ability may actually enhance lung localization of blood-borne microparticles, which have a high affinity for fibronectin.
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PMID:Comparative effect of circulating bacterial or nonbacterial particulates on plasma fibronectin: relationship to lung deposition of blood-borne foreign particles. 374 38

Behavioral effects of bilateral intracranial infusions of tetrodotoxin (1, 3.3 or 10 ng/rat), 50% procaine (2 microliters/rat) or phosphate-buffered saline (PBS-2 microliters/rat) into the dorsal midbrain of conscious, lightly-restrained female rats were evaluated. High levels of lordotic responsiveness were induced in ovariectomized animals treated with estradiol (E2) capsules or subcutaneous injections of estradiol benzoate (EB) followed by progesterone (P). The effect of each of the 3 infusates on lordosis was determined using manual stimulation and lordosis quotient determinations. In addition, the vocalization by an animal during lordosis measurements, paw withdrawal to pinch, righting reflex latency and recognition of a platform edge were also monitored. Within 2 minutes following procaine or tetrodotoxin (TTX) infusions in E2 implanted rats, lordotic responsiveness declined sharply. Whereas procaine-treated animals returned to control levels of responsiveness within 20 minutes, TTX infusions induced a more prolonged depression of lordosis lasting up to 8 hours. Infusions of PBS had no effect on any of the behaviors. In a separate group of animals treated with either E2 or EB + P and infused with 10 ng TTX the time course of the decline in lordotic responsiveness was identical for both steroid treatments. Paw withdrawal was unaffected by TTX while all other measured behaviors were disrupted along the same time course as lordosis. Collectively the above results implicate the requirement of sodium-dependent neuronal activity within dorsal midbrain for the maintenance of the lordosis reflex, along with other behavioral responses influenced by this brain region.
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PMID:Reversible disruption of lordosis via midbrain infusions of procaine and tetrodotoxin. 378 44

Plagemann, Peter G. W. (Western Reserve University, Cleveland, Ohio), and H. Earle Swim. Replication of mengovirus. I. Effect on synthesis of macromolecules by host cell. J. Bacteriol. 91:2317-2326. 1966.-The replication of mengovirus was studied in two strains of Novikoff (rat) hepatoma cells propagated in vitro. The replicative cycle in both strains required 6.5 to 7 hr. Infection resulted in a marked depression of ribonucleic acid (RNA) and protein synthesis by strain N1S1-63. Inhibition of RNA synthesis was reflected by a decrease in the deoxyribonucleic acid (DNA)-dependent RNA polymerase activity of isolated nuclei. Mengovirus had no effect on either protein or RNA synthesis or on the DNA-dependent RNA polymerase activity of a second strain, N1S1-67. The time course of viral-induced synthesis of RNA by cells was studied in cells treated with actinomycin D. It was first detectable between 2.5 and 3 hr after infection and continued until 6.5 to 7 hr. The formation of mature virus was estimated biochemically by measuring the amount of RNA synthesized as a result of viral infection which was resistant to degradation by ribonuclease in the presence of deoxycholate. Approximately 70% of the deoxycholate-ribonuclease-resistant RNA was located in mature virus, and the remainder was double-stranded. The formation of mature virus began about 45 min after viral-directed (actinomycin-resistant) synthesis of RNA was detectable in the cell, and only about 18 to 20% of the total RNA synthesized was incorporated into virus. Release of virus from cells began about 1 hr after maturation was first detectable. Release of virus from cells was accompanied by a loss of a large proportion of their cytoplasmic RNA and protein.
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PMID:Replication of mengovirus. I. Effect on synthesis of macromolecules by host cell. 428 85

Tyrosine hydroxylase (TH) levels in the rat neostriatum are decreased by chronic treatment with methamphetamine. GABAergic neurons could potentially interact with the nigrostriatal dopaminergic neurons in either the neostriatum or the substantia nigra; therefore, the GABA transaminase inhibitors, amino-oxyacetic acid, gamma-acetylenic GABA and ethanolamine-O-sulfate, were evaluated for possible influences on the methamphetamine-induced decrease in TH. TH was measured by the procedure of Nagatsu et al. (1964). Methamphetamine (10 mg/kg, s.c.) was given every 6 h for 24 h. Thirty-six h after initiation of the methamphetamine treatment, neostriatal TH activity was approximately 70% of control. Concurrent administration of amino-oxyacetic acid (20 mg/kg, i.p.) or gamma-acetylenic GABA (15 mg/kg, i.p.) with methamphetamine completely blocked the TH depression. Dose-response curves were constructed for amino-oxyacetic acid and gamma-acetylenic GABA. A single intraventricular injection of ethanolamine-O-sulfate (400 micrograms/rat), 2-6 h before initiating the methamphetamine regimen, also completely blocked the TH depression. These data suggest that the striatonigral or other GABAergic systems are involved in the regulation of the functional state of the nigrostriatal dopaminergic neurons, and that enhanced GABAergic function will antagonize the effects of high doses of methamphetamine.
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PMID:Blockade of methamphetamine-induced depression of tyrosine hydroxylase by GABA transaminase inhibitors. 610 24

Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 microgram to 100 micrograms per rat (ED 50: 1.5 microgram/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 microgram to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 micrograms/rat) or i.p. (0.5 mg/kg) injections of naloxone.
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PMID:Intrathecal substance P depresses the tail-flick response - antagonism by naloxone. 617 Aug 95

This study deals with the effects of beta-endorphin on blood pressure, heart rate, and respiratory frequency in anesthetized and conscious rats after both peripheral and central administration. Intravenous injection of beta-endorphin (40 and 160 micrograms/kg) in urethane-anesthetized rats resulted in a prolonged decrease in blood pressure, which, after the higher dose, was accompanied by bradycardia. In the pentobarbitone-anesthetized animals the same doses of beta-endorphin caused a small rise in blood pressure without affecting heart rate. No effect on respiratory frequency was observed. In urethane-anesthetized rats with hemorrhagic shock intravenous naloxone elicited a small pressor effect. Intracerebroventricular injection (i.c.v.) of beta-endorphin (40 micrograms/rat) in urethane-anesthetized rats resulted in severe respiratory depression and death. With lower doses there was a decrease in all parameters studied without ensuing death. Respiratory depression was even more pronounced in pentobarbitone-anesthetized rats, occurring with much lower doses of the peptide than in the urethane-anesthetized animals. beta-endorphin in the dose of 0.6 micrograms/rat still reduced respiratory frequency as well as heart rate without affecting blood pressure. Naloxone pretreatment antagonized the respiratory depression and death, while the decrease in heart rate was diminished. In conscious rats 10 microgram/rat, i.c.v., of beta-endorphin resulted in a decrease in heart rate and blood pressure without affecting respiratory frequency. It is concluded that beta-endorphin, or related opioid peptides, may be involved in cardiovascular and respiratory regulation. The effects of beta-endorphin, however, are markedly modified by the anesthetic agent used.
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PMID:Cardiovascular and respiratory effects of beta-endorphin in anesthetized and conscious rats. 618 78

The effect of the teratogen 2-amino-1,3,4-thiadiazole on glycogenesis and glycogenolysis was investigated in the fetal and neonatal rat liver. At day 15, 16, or 17 of gestation (sperm day = day 0) pregnant Sprague-Dawley rats received a single IP injection of an aqueous solution of aminothiadiazole. Dosages used were teratogenic (100 mg/kg maternal body weight) and nonteratogenic (10 mg/kg). At day 16 some rats received nicotinamide (100 mg/rat) in addition to a teratogenic dose of aminothiadiazole. Livers were recovered for assay at fetal day 20 and postnatal day 1. Only at day 16 did a teratogenic dose induce a significant depression in the fetal activity of glycogen synthetase (to 49.6% of control activity) and glucose-6-phosphatase (to 72.2% of control activity), and in glycogen accumulation (to 72.6% of control accumulation). At day 15, a teratogenic dose significantly depressed glucose-6-phosphatase activity but not glycogen synthetase activity or glycogen accumulation. Nicotinamide, given immediately after aminothiadiazole, was effective in blocking the inhibition. Teratogenic treatment had no effect on the postnatal activity of glucose-6-phosphatase. Apparently some event associated with birth releases the enzyme from its prenatal inhibition. These results demonstrate a parallelism between the perturbing effect of aminothiadiazole on biochemical development and morphological development with respect to time of insult, dose response, and protection with its antiteratogen. The mechanism of action whereby aminothiadiazole depresses the activity of glycogen synthetase and glucose-6-phosphatase remains to be determined.
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PMID:The effect of aminothiadiazole on glycogenesis and glycogenolysis in fetal and neonatal rat liver. 632 Apr 84


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