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PubMed1991

Evidence for the existence of a urethro-urethral excitatory reflex in urethane anesthetized rats: involvement of peripheral ganglionic structures.

In urethane-anesthetized rats urethral distension with saline at the level of the external urethral sphincter elicited a series of slow phasic contractions with an amplitude between two and 18 mm. Hg. Contractions having an amplitude lower than four mm Hg were unaffected by i.v. or topical hexamethonium (HEX) or by topical tetrodotoxin (TTX). HEX or TTX transiently abolished or reduced the distension-evoked contractions having an amplitude between four and 18 mm. Hg. Administration of d-tubocurarine (d-Tc), atropine, bilateral section of pudendal nerves, spinalization (T12-S1) or bilateral removal of the major pelvic ganglia did not modify the distension-induced rhythmic urethral activity. In rats desensitized to capsaicin (four days before), both amplitude and frequency of urethral contractions did not differ from control value. In rats pretreated with atropine, administration of HEX still inhibited the distension-induced urethral contractions. Intravenous dimethylphenylpiperazinium (DMPP) triggered a rapid phasic contraction with an amplitude ranging between 15 and 25 mm. Hg. This effect was inhibited by previous administration of HEX. In accordance with histochemical studies showing spherical ganglionic cell bodies between the outermost striated muscle layer and the smooth muscular coat, present data indicate that distension of the external urethral sphincter reflexly activates urethral contractions, possibly through a local mechanism.

Anesthesia↗
PubMed1985

The effect of cyclooxygenase inhibitors on the low filling rate cystometrogram in urethane anesthetized rats.

The effect of two widely used cyclooxygenase inhibitors (indomethacin and ketoprofen) on the low filling rate cystometrogram was investigated in urethane anesthetized rats. Both indomethacin and ketoprofen significantly increased volume threshold to elicit neurogenic bladder contractions without affecting their amplitude. Also the pressure threshold was unaffected by both drugs while the volume/pressure relationship was significantly flattened compared to controls. These findings indicate that acute suppression of arachidonic acid metabolism along the cyclooxygenase pathway increases the micturition threshold without affecting bladder muscle contractility and/or neurotransmission along the efferent pathway of the micturition reflex.

Anesthesia↗
PubMed1985

The effect of capsaicin pretreatment on the cystometrograms of urethane anesthetized rats.

Administration of capsaicin to newborn rats produced a slight but significant increase in bladder weight and markedly altered the cystometrograms of urethane anesthetized rats. In particular capsaicin pretreatment significantly increase micturition threshold. In many of these preparations the bladders exhibited a hypertonic response to saline filling; the flat phase of the cystometrogram was not observed. Capsaicin pretreatment of adult animals increased micturition threshold up to 1 month from capsaicin administration. In these preparations a flat volume-pressure relationship preceded micturition contractions. Administration of capsaicin to both newborn and adult animals did not alter the amplitude of micturition contractions. Intravesical installation of capsaicin had an acute excitatory effect on the responsiveness of the urinary bladder to reflex activation. These findings indicate that capsaicin pretreatment produces a functional impairment of the sensory branch of micturition reflexes and suggest that a capsaicin-sensitive mechanism(s) is involved in the regulation of micturition threshold.

Anesthesia, General↗
PubMed2001

Can conditioned histamine release occur under urethane anesthesia in guinea pigs?

Many clinical and experimental data have shown that learning can occur under general anesthesia. To clarify this possibility with respect to allergic reactions, particularly asthmatic responses, we first established classical conditioned histamine release in response to a neutral odor by using pairings of the odor and an inhaled antigen for five sessions (Experiment 1) and then investigated whether conditioned histamine release into the plasma, bronchoalveolar lavage fluid (BALF), and lung tissue, which followed such a conditioning procedure, would be produced in urethane-anesthetized guinea pigs in the presence or absence of antigen (Experiment 2). Ovalbumin (OA) was used as the unconditioned stimulus (US) and dimethylsulfide (DMS) served as the conditioned stimulus (CS) in both experiments. In Experiment 1, the plasma histamine levels in the conditioned group increased significantly more than those of the unpaired control group in response to the CS during consciousness. In Experiment 2 in the absence of antigen, however, no significant differences in the histamine levels were found regarding the groups (DMS, triethylamine, saline, or unsensitized) or the time course (before, immediately, 5 min, and 10 min after the inhalations) during anesthesia, except for the finding that the histamine levels in the lung tissue specimens from the DMS group were significantly higher than those from the triethylamine group. In Experiment 2 in the presence of antigen, there was a significant increase in the plasma histamine levels after exposure to the US, irrespective of the presence of the CS, however, no significant difference in the histamine levels was observed between the US and the CS+US groups. These results indicated that a classically CS might not induce asthmatic responses under anesthesia.

Anesthesia, Intravenous↗
PubMed1998

Indian red scorpion (Buthus tamulus) venom-induced augmentation of cardiac reflexes is mediated through the mechanisms involving kinins in urethane anaesthetized rats.

The mechanism underlying the action of Indian red scorpion (Buthus tamulus; BT) venom on cardiac reflexes was examined in urethane anaesthetized adult albino rats of either sex. Intravenous injection of phenyldiguanide (PDG) produced reflex hypotension, bradycardia and apnea lasting for > 60 s. The PDG-induced reflex responses (blood pressure, heart rate and respiration) were augmented greatly (magnitude and time period) after exposure to BT venom (100 microg/kg, i.v., for 30 min). However, there were no great alterations in resting blood pressure, heart rate and respiratory rate. Pretreatment with kallikrein kinin inhibitor (aprotinin; 6000 kallikrein inactivating unit, i.v.) blocked the BT venom-induced augmentation of PDG reflex response. Further, pretreatment with indomethacin (prostaglandin synthetase inhibitor; 10 mg/kg) and heparin (1000 units/kg) also blocked the venom-induced potentiation of the reflex. Captopril (15 mg/kg), an agent known to increase endogenous kinins, also augmented the PDG induced-reflex to the same extent as in BT envenomed rats. The captopril-induced augmentation of the reflex was blocked by aprotinin and heparin, but not by indomethacin. The results indicate that kinins and prostaglandins are involved in the BT venom-induced augmentation of the cardiac reflexes.

Analgesics↗
PubMed2003

Silk fibroin/poly(carbonate)-urethane as a substrate for cell growth: in vitro interactions with human cells.

Silk fibroin (SF)-based or -coated biomaterials are likely to be endowed with structural and surface properties that render them particularly apt for biomedical applications. In this work we investigated the behavior of four different strains of normal human adult fibroblasts that had been seeded onto membranes made up of poly(carbonate) urethane (PCU), the surfaces of which had or had not been homogeneously coated with SF. Cell adhesion within 3h to the SF-coated PCU films was 2.2-fold that to their uncoated homologues. After 30 days of incubation in vitro, 2.5-fold more cells had grown on the SF-coated specimens than on the uncoated ones. This enhanced cell adherence and hence growth on the SF-coated surfaces was coupled with higher cumulative rates of D-glucose (but not L-glutamine) uptake and of both lactate and interleukin-6 (IL-6) cumulative secretion. Conversely, human fibroblasts cultured on either type of PCU scaffolds never secreted any ELISA-assayable amount of three main proinflammatory cytokines, namely interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1). Finally, when the metabolic activities were compared on a per 10(5) cells basis, it became clear that the adhesion to SF favored an initially higher consumption of D-glucose, a late higher release of IL-6, and an at-first more intense, but declining, extracellular assembly of type I collagen fibers. Overall, these results show that SF-coated PCU membranes represent a novel type of biomaterial that favors the adhesion, the growth and performance of specific metabolic tasks by normal human adult fibroblasts without eliciting any concurrent secretion of some of the chief proinflammatory cytokines.

Adult↗
PubMed1998

Effects of dexmedetomidine, an alpha2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits.

To clarify the role of the neural blood pressure control system in hemodynamic changes after dexmedetomidine (DXM) administration, we examined the effects of an intravenous injection of DXM (10 microg/kg) on heart rate (HR), mean blood pressure (MBP), central venous pressure (CVP) and renal sympathetic nerve activity (RNA) in urethane-anesthetized rabbits using direct recordings of RNA. The animals were divided into four groups: animals with an intact neuraxis (intact group; n = 12), cervical vagotomized animals (vagotomy group; n = 5), sino-aortic denervated animals (SAD group; n = 5), and animals with SAD plus vagotomy (SADV group; n = 5). An initial HR decrease, which occurred in the intact group, did not occur in the other three groups, suggesting the mediation of the baroreflex. A subsequent HR decrease occurred in the three groups other than the vagotomy group, in which RNA recovered earlier than in the other groups. RNA in the intact group, associated with transient hypertension, was suppressed shortly after the injection. Such an RNA drop was not eliminated even in the SADV group. Despite recovery of RNA, hypotension lasted until the end of experiment in the intact and vagotomy groups. However, sustained depression of RNA associated with lasting hypotension was found in the SAD and SADV groups. CVP in all groups did not change significantly after the injection. These results suggest the following: (1) Initial bradycardia after DXM is mediated via the baroreflex. Subsequently, HR reductions may result mainly from central sympathetic depression. (2) An initial reduction in RNA is not mediated via the baroreceptor reflex, unlike HR responses, but by central sympatho-inhibitory effects. (3) Long-lasting hypotension after DXM is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic alpha2-adrenoceptors, rather than to central sympathetic depression.

Adrenergic alpha-Agonists↗
PubMed1997

Excitatory action of angiotensins II and IV on hippocampal neuronal activity in urethane anesthetized rats.

The renin-angiotensin system of the mammalian brain seems to interfere with the process of cognition and has been associated with the hippocampal function in relation to mechanisms of learning and memory. In our investigation, the effects of angiotensin II (Ang II) and angiotensin IV (Ang II) on neuronal activity have been studied in the hippocampus of adult rats anesthetized with urethane. Excitatory effects of both angiotensins predominated over inhibitory effects. Angiotensins also induced an enhancement of burst discharges. These angiotensin-induced effects were blocked by the specific angiotensin antagonists. Our findings showed that the different effects of Ang II and Ang IV in behavioral studies are not similarly reflected in a different change of the discharge rate and/or pattern of hippocampal neurons after microiontophoretic administration of both substances.

Action Potentials↗
PubMed1978

Two crops of primary lung tumors in BALB/c mice after a single transplacental exposure to urethane.

Transplacental exposure of BALB/c mice to urethane on day 17 of gestation resulted in the appearance of 2 distinct crops of primary lung tumors (adenomas). The first, smaller crop occurred in 6--12% of the offspring by 12 weeks of age. The second crop, seen after 9 months of age, consisted of tumors in 45% of the offspring. This finding indicates a potentially useful model system for studying tumor latency. It also suggests caution in the choice of short endpoints in time carcinogenesis assays based on lung tumors in certain strains of mouse.

Adenoma↗
PubMed1998

Pulmonary fibrosis caused by N-methyl-N-nitrosourethane inhibits lung tumorigenesis by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

Male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) received three subcutaneous injections of 0.3 mg N-methyl-N-nitrosourethane (MNUR) once every 2 weeks for the first 4 weeks followed by a single intraperitoneal injection of 1000 or 0 mg/kg urethane (UR) 2 weeks later. They were then maintained without any other treatment for a further 13 weeks and sacrificed for assessment of pulmonary pathology. Inflammatory lesions, such as macrophage infiltration, alveolar bronchiolization and/or fibrosis, were induced in both rasH2 and non-Tg mice treated with MNUR or MNUR + UR. Lung proliferative lesions were induced in 100% of the UR-treated rasH2 mice but to a significantly lesser extent in the MNUR + UR case. The incidences of lung tumors in non-Tg mice treated with UR or MNUR + UR were relatively low. Point mutations of the transgene were detected in approximately 80% of lung tumors in rasH2 mice treated with UR and MNUR + UR, but murine Ki-ras mutations were rare. No marked difference in the mutation pattern was found between the UR-treated and the MNUR + UR-treated rasH2 mice. In non-Tg mice treated with UR or MNUR + UR, point mutations of the murine c-Ki-ras gene were observed in about 50% of the lung tumors examined. The present study confirmed that rasH2 mice are very sensitive to lung tumor induction by UR and suggested that alveolar epithelial cells in the reparative stage during pulmonary fibrosis are resistant to DNA damage by this carcinogen.

Animals↗
PubMed2000

Differential activation of Fos-like immunoreactivity in the arcuate nucleus and amygdala after intracerebroventricular injection of sodium nitroprusside and N omega nitro-L-arginine in conscious and urethane-anesthetized lactating rats.

The effect of intracerebroventricular injection of a nitric oxide (NO) donor (sodium nitroprusside, SNP) or NO synthase inhibitor (N(omega) nitro-L-arginine, L-NA) on Fos-like immunoreactivity (FLI) in the arcuate nucleus (ARC) and the medial, cortical and central amygdaloid nuclei was examined in conscious and urethane-anesthetized lactating rats. In conscious dams, the number of FLI-cells in the medial and cortical amygdaloid nuclei were significantly larger after the injection of L-NA than after SNP injection. In anesthetized dams, the number of FLI-cells was decreased in the medial and cortical amygdaloid nuclei by L-NA injection, whereas the numbers were increased in the ARC and the medial amygdaloid nuclei after the injection of SNP. The nucleus-specific response to SNP or L-NA suggested possible involvement of NO in modulation of dynamics of neuronal activity within these nuclei.

Amygdala↗
PubMed1997

Effect of alpha 1-adrenoceptor antagonists on urinary bladder function in urethane-anesthetized rats.

1. We investigated the effects of selective alpha 1-adrenoceptor antagonists on rhythmic bladder contraction and cystometrograms as representative of urinary bladder function in urethane-anesthetized rats. 2. The selective alpha 1-adrenoceptor antagonists tamsulosin (0.03-3 micrograms/kg IV), prazosin (0.03-3 micrograms/ kg IV) and bunazosin (0.03-3 micrograms/kg IV) exerted little effect on the amplitude and frequency of rhythmic bladder contraction in anesthetized rats. In contrast, the antipollakiuria agent flavoxate (5 and 10 mg/kg IV) induced a dose-dependent disappearance in frequency without affecting the amplitude of the contractions. 3. Tamsulosin (1 and 3 micrograms/kg IV), prazosin (1 and 3 micrograms/kg IV), and bunazosin (1 and 3 micrograms/kg IV) exerted no effect on the cystometrogram, either. However, flavoxate (5 and 10 mg/kg IV) raised the micturition threshold pressure and prolonged the time to micturition. 4. These results suggest that the alpha 1-adrenoceptor plays little role in urinary bladder contraction in anesthetized rats.

Adrenergic alpha-Antagonists↗
PubMed1998

Comparison of responses of spontaneously active cells in the cerebellar Purkinje layer to parallel fibre stimulation in slice preparations and urethane-anaesthetised rats: effects of benzodiazepine receptor ligands.

1. GABA-mediated inhibitory responses were induced in spontaneously active Purkinje cells by parallel fibre stimulation in cerebellar slices or in urethane-anaesthetised rats. Effects of agonist and inverse agonist benzodiazepine (BDZ) receptor ligands were compared in the preparations. 2. Purkinje cells fired simple spikes at higher rates in slice preparations while complex spikes were seldom (in vivo) or never observed (slice). Cells fired more regularly in vivo resulting in the occurrence of rhythmic postinhibitory responses in the PSTH analysis in some preparations. 3. Single pulse stimulation of parallel fibres at just suprathreshold intensity induced inhibition of Purkinje cell activity in both preparations. At lower firing rates there was a marked increase in the duration of this response, which was more evident in vivo where more slowly firing cells were encountered. 4. BDZ receptor ligands modified inhibitory responses in slice preparations with only weak effects on the firing rates of the cells. These compounds predominately induced changes in firing rate in the anaesthetised rat with little evidence of direct modification of GABA-mediated synaptic transmission. 5. In a few experiments, following injection of the partial inverse agonists beta-CCE and beta-CCM, block of the inhibitory response was observed independent of changes in firing rate. Bidirectional efficacy of BDZ receptor ligand (agonists decrease firing and increase inhibitory response, inverse agonists increase firing and decrease inhibitory response) was demonstrated for modulation of inhibitory responses in slices and for changes in firing rate in vivo. The increased firing rate response in vivo was biphasic the magnitude of the later phase being correlated with efficacy of inverse agonists. 6. It is concluded that cerebellar slice preparations are more appropriate for studying direct effects of BDZ receptor ligands on GABA-mediated synaptic inhibition than in vivo preparations.

Action Potentials↗
PubMed2003

Integrated contributions of basal forebrain and thalamus to neocortical activation elicited by pedunculopontine tegmental stimulation in urethane-anesthetized rats.

Efferents from the pedunculopontine tegmentum (PPTg) exert widespread control over neocortical electrocorticographic (ECoG) activity and aid in maintaining high-frequency ECoG activation during waking and rapid eye movement sleep. The mechanisms and subcortical routes that allow the PPTg to influence cortical activity remain controversial. We examined the relative contributions of the thalamus and basal forebrain in ECoG activation elicited by PPTg stimulation in urethane-anesthetized rats. Stimulation (100 Hz, 2 s) of the PPTg suppressed large-amplitude, low-frequency oscillations, replacing them with high-frequency beta-gamma activity. Systemic administration of the anti-muscarinic drug scopolamine (1 mg/kg, i.p.) abolished activation elicited by PPTg stimulation, suggestive of an essential role of acetylcholine in this effect. Local infusions of lidocaine (1 microl, 1%) into the region of the cholinergic basal forebrain complex produced a strong reduction in activation elicited by PPTg stimulation. Lidocaine infusions into the reticular thalamic nucleus had no effect, but infusions into central thalamus produced a small attenuation of PPTg-evoked cortical activation. Combined basal forebrain-central thalamic infusions (1 microl/site) produced roughly additive effects, leading to a greater loss of activation than single-site infusions. These results indicate that, under the present experimental conditions, high-frequency cortical ECoG activation elicited by the PPTg involves relays in both the basal forebrain and central thalamus, with a predominant role of the basal forebrain. After concurrent central thalamic-basal forebrain inactivation, the forebrain can maintain only limited, short-lasting activation in response to PPTg stimulation. The additivity of infusion effects suggests that, rather than participating in one serial system, basal forebrain and central thalamus constitute parallel activating pathways. These findings aid in resolving previous controversies regarding the role of thalamus and basal forebrain in activation by emphasizing the importance of multiple, large-scale networks between brainstem and cortex in regulating the activation state of the mammalian neocortex.

Acetylcholine↗
PubMed1998

The effect of chemoreceptor stimulation on the centripetal transfer of somatosensory information in the urethane-anaesthetized rat.

In urethane-anaesthetized rats, stimulation of carotid body chemoreceptors desynchronizes the cortical electroencephalogram and increases the sensitivity of thalamic and cortical somatosensory neurones to peripheral sensory nerve stimulation. Peripheral chemoreceptors were stimulated by injecting a bolus (30 ml) or infusing 100 ml of 0.18 M NaCl solution equilibrated with 100% CO2 into an internal carotid artery, the cortical electroencephalogram and ventilation were monitored routinely. This stimulus induced hyperventilation and desynchronization of the cortical electroencephalogram. Anaesthetized rats also showed spontaneous periodic increases in ventilation rate accompanied by changes of the cortical electroencephalogram from high-voltage low frequency to low-voltage high frequency which seemed to be identical with those evoked by stimulating chemoreceptors. The activity of identified somatosensory neurons in the thalamic ventrobasal complex, layer IV of the somatosensory cortex, or the cuneate nucleus was recorded extracellularly during and following chemoreceptor activation. Neurones in the ventrobasal thalamus and somatosensory cortex showed a decrease in latency and an increase in probability of discharge to supramaximal electrical stimulation of the forepaw which was more pronounced following infusion stimulation of the carotid body than following bolus stimulation. In contrast, neurons within the cuneate nucleus showed a slight increase in latency to onset and a decrease in the probability of firing following the same stimulus. The results indicate that stimulation of the carotid body chemoreceptors leads to an enhancement of the response of somatosensory neurons to their normal physiological input.

Anesthetics, Intravenous↗
PubMed2002

Microinjection of procaine into the pedunculopontine tegmental nucleus suppresses hippocampal theta rhythm in urethane-anesthetized rats.

It was found that the cholinergic component of the pedunculopontine tegmental nucleus (PPN) is involved in the generation of theta rhythm in the hippocampus. However, it is still not known how important PPN is in the brainstem theta-generating system, where the nucleus reticularis pontis oralis is regarded as a primary generator. In the present experiment, performed on urethane-anesthetized rats, we studied the effect on the tail pinch-elicited hippocampal theta of unilateral inactivation of PPN by means of direct procaine microinjection. Procaine induced ipsilateral suppression of theta rhythm, manifested as desynchronization of hippocampal EEG, a shift of the fast Fourier transformation (FFT) power peak toward lower frequencies, and a reduction of FFT peak magnitude at theta band. Hippocampal field activity returned to normal (both its FFT peak frequency and magnitude) within 30 min after the injection. The results obtained indicate that PPN is critical for hippocampal theta generation but it may not be involved in encoding theta frequency.

Anesthetics, Intravenous↗
PubMed1996

In vivo evaluation of a fluorine-acryl-stylene-urethane-silicone antithrombogenic coating material copolymer for intravascular stents.

RATIONALE AND OBJECTIVES: We evaluated the effectiveness of a fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer as an antithrombogenic coating material for intravascular stents in dogs. METHODS: FASUS copolymer-coated stents were placed in the right iliac veins, and uncoated 304 stainless steel stents were placed in the left iliac veins. We examined platelet deposition, microthrombus formation, and neointimal hyperplasia 4 weeks after stent placement by measuring the activity of 111In-labeled platelets, by using scanning electron microscopy, and by measuring neointimal thickness. RESULTS: Platelet deposition was significantly decreased on coated than on uncoated stents (p < .05). A less pronounced increase in red blood cell deposition was observed at the sites of the coated than uncoated stents (p < .05). Neointimal thickness 4 weeks after stent placement also was significantly less at the sites of the coated stents (0.27 +/- 0.08 mm versus 0.48 +/- 0.23 mm, p < .05). CONCLUSION: FASUS copolymer coating over the vascular stent is effective for preventing thrombus formation and neointimal hyperplasia.

Animals↗
PubMed1998

In vivo antigenotoxic effects of dietary agents and beverages co-administered with urethane: assessment of the role of glutathione S-transferase activity.

Antigenotoxic effects and changes in glutathione S-transferase (GST) activity were assessed in mice after oral co-administration of urethane (URE) with aqueous extracts of dietary vegetables (carrot, spinach and cabbage), spices (cinnamon, pepper, cumin, clove and cardamom), tea and coffee. The results of the genotoxicity assay (micronucleus test) demonstrated dose-related antigenotoxic effects after URE was co-administered with aqueous extracts of vegetables, spices, tea and coffee. Inhibition of GST activity was observed 4 h after treatment with URE alone. Co-administration of URE with extracts of vegetables, coffee and spices resulted in dose-related attenuation of the inhibitory effect of URE on GST activity. However, tea had no effect on inhibition of GST activity by URE. Hence an association between antigenotoxicity and GST activity could not be established.

Animals↗