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PubMed1994

Very slow oscillations of activity in geniculate neurones of urethane-anaesthetized rats.

The spontaneous activity of neurones of the dorsal lateral geniculate nucleus (dLGN) in urethane-anaesthetized rats was examined for the presence of very slow oscillatory activity. Fifty-four of the 86 dLGN neurones (63%) recorded extracellularly displayed oscillatory activity in the 0.02-0.03 Hz range. Similar very slow oscillations were observed in the ventral part of the LGN and the nucleus lateralis posterior (LP), but not in the hippocampus. Diffuse light stimuli dampened or blocked these oscillations in 23 of the 29 neurones tested. In a second group of experiments (iontophoretic studies) the very slow oscillatory activity was efficiently blocked by N-methyl-D-aspartate.

Action Potentials↗
PubMed1996

Midbrain raphe cell firing and hippocampal theta rhythm in urethane-anaesthetized rats.

This study aimed to examine the functional coupling between midbrain raphe and the septohippocampal system at the level of neuronal firing. Raphe unit activity and hippocampal EEG were simultaneously recorded in urethane-anaesthetized rats and their relationship was examined in the frequency domain. Subsets of presumably non-serotonergic neurones in both the dorsal and median raphe nuclei fired rhythmically in synchrony with hippocampal theta activity. Theta cells in the median raphe showed higher coherence than those in dorsal raphe and formed a more homogeneous group of cells, according to their firing rates. Since the raphe-septal serotonergic system is known to desynchronize the hippocampal EEG, activation of a subset of nonserotonergic cells during theta in this nucleus indicates a feedback from the limbic circuitry on the ascending raphe control of forebrain activity.

Anesthesia, General↗
PubMed2000

Effects of induced hypothermia on renal sympathetic nerve activity and baroreceptor reflex in urethane-anesthetized rabbits.

OBJECTIVE: To evaluate the role of the autonomic nervous system in hemodynamic changes during induced hypothermia. DESIGN: Prospective, randomized animal study. SETTING: An animal research laboratory in a medical university. SUBJECTS: A total of 29 anesthetized rabbits. INTERVENTIONS: Animals were anesthetized by intraperitoneal urethane. After tracheostomy and administration of gallamine, respiration was maintained by mechanical ventilatory support. The animals were divided into five groups (one control and the four experimental groups); animals were treated with an intact neuraxis and normothermia (control group), animals with an intact neuraxis (intact group), cervical vagotomized animals (vagotomy group), the carotid sinus and aortic nerves denervated animals (SAD group), and animals with SAD plus vagotomy (SADV group). The left renal sympathetic nerves were exposed by a retroperitoneal approach. MEASUREMENTS AND MAIN RESULTS: We examined the effects of surface cooling on HR, mean arterial pressure, central venous pressure, and renal sympathetic nerve activity (RSNA) in the animals. Changes of baroreflex sensitivity and plasma catecholamines were also measured simultaneously. Surface cooling caused progressive and profound decreases in HR in all experimental groups. In all groups, RSNAs increased at the early phase, which were followed by return to the precooling level. CONCLUSIONS: Hemodynamics and RSNA during induced hypothermia are regulated by mechanisms other than the baroreceptor reflex system, possibly the dermal cold receptors. Suppression of the baroreflex occurred on HR but not on RSNA during hypothermia, which may indicate direct effects of hypothermia on the heart. RSNA responses may be activated earlier than systemic catecholamine responses during induced hypothermia.

Adrenergic Fibers↗
PubMed1984

Mandibular reconstruction using the Dacron-urethane prosthesis and autogenic cancellous bone: review of 32 cases.

The prosthesis and cancellous bone graft technique has proven to be versatile, reliable, and highly successful when applied to mandibular reconstruction. The type of prosthesis used appears to be of some importance. Analysis of 32 cases in which the Dacron-urethane mandibular prosthesis was used is presented. Among these cases there were one failure (3 percent) and three minor complications (9 percent). These results are superior to those reported in the series in which metallic prostheses were used.

Adolescent↗
PubMed1997

Urethane-protected N-carboxyanhydrides (UNCAs) as unique reactants for the study of intrinsic racemization tendencies in peptide synthesis.

We have established that urethane-protected N-carboxyanhydrides (UNCAs) are uniquely suited for the study of intrinsic racemization tendencies in peptide synthesis. The UNCA allows epimerization only by the direct enolization pathway (Proton abstraction from the alpha-carbon) and does not decompose upon epimerization. A protocol employing the quantitative separation and analysis of enantiomeric N-protected amino acid derivatives by chiral HPLC has been developed to measure the intrinsic rate of racemization of UNCAs under widely varying reaction conditions. The influence of the tertiary amine structure, UNCA side chain structure, and solvent were studied. The same protocol was employed to study the intrinsic rate of racemization of N-protected activated amino acid intermediates generated via 'onium-type' activating reagents. We have shown that the trends influencing the intrinsic rate of racemization of UNCAs are maintained under the conditions of in situ activations, and are consistent with the trends found in classical studies in the literature. The results are relevant to peptide synthesis both in solution and on solid phase. The intrinsic rate of racemization for any type of activation with any tertiary amine can be measured by this protocol.

Amino Acids↗
PubMed1997

Responses of cortical EEG-related basal forebrain neurons to brainstem and sensory stimulation in urethane-anaesthetized rats.

The basal forebrain can be considered to be a rostral extension of the ascending reticular activating system. A large number of neurons in the basal forebrain have been shown to display higher firing rates when low-voltage fast activity is present in the cortical EEG as opposed to states characterized by large slow waves in both unanaesthetized and anaesthetized animals. However, a smaller number of cells with increased discharge rate during slow waves was also observed in most of these studies. While it is likely that these two types of neurons have opposite roles in the regulation of cortical activation, it is not known how they respond to inputs from the brainstem or the periphery. In the present study, extracellular recordings were made in the basal forebrain of urethane-anaesthetized rats. A total of 52 neurons were studied in which the firing rate was significantly higher during fast cortical EEG waves (F-cells), and 14 neurons in which activity was significantly greater during slow waves (S-cells). The two cell types responded differently to stimulation of the pedunculopontine tegmental nucleus (PPT) and dorsal raphe nucleus (DRN) with short (0.5-1 s) trains of pulses and to noxious sensory stimuli (tail pinch). These stimulations excited most F-cells (80-96%) and inhibited the majority of S-cells (55-67%). In the few F-cells that were inhibited by stimulation, the response varied with the background firing rate of the cell: the higher the firing rate at the time of stimulation, the higher the probability of observing an inhibitory response. In contrast, single electrical pulses delivered to the PPT and DRN excited the majority (72%) of both F- and S-cells. Previous in vitro studies have shown that the application of acetylcholine or serotonin has predominantly inhibitory effects on basal forebrain cholinergic neurons. The predominantly excitatory effect of noxious, PPT and DRN stimulation on F-cells therefore suggests that glutamatergic or other excitatory afferents play a more dominant role in regulating basal forebrain neurons. We have previously shown that F-cells are more prevalent than S-cells. In combination, these findings suggest that basal forebrain neurons, and F-cells in particular, are important in mediating the ascending excitatory drive from the brainstem to the cerebral cortex.

Anesthesia, General↗
PubMed1978

The effects of pentobarbitone and urethane on pulmonary airway resistance in guinea-pigs and their interactions with drugs.

1 Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea-pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone. 2 The direct bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine. 3 Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were potentiated by pentobarbitone. 4 Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments. 5 Like pentobarbitone, urethane increased PAR in the conscious guinea-pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.

Airway Resistance↗
PubMed1984

The action of dantrolene sodium on individual fast and slow motor units of the rat anaesthetized with urethane.

Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a vehicle of 5% mannitol taken to pH 10 with NaOH. The muscle relaxant action of dantrolene sodium was measured from the contractions of individual motor units of the extensor digitorum longus (EDL), soleus (SOL) and segmental tail (ST) muscles. Data were also collected from their parent whole muscle preparations. The depressant action of dantrolene sodium on the percentage-normalized amplitude of contraction of the individual motor units was greater than its effect on the whole muscle twitch amplitude, in all three muscles. The twitch amplitude of fast contracting motor units was significantly more reduced (P less than 0.001) by dantrolene sodium than was that of slow contracting motor units. Dantrolene sodium reduced the contraction time of all motor units. The effect of the drug on half-relaxation time varied within and between groups of motor units studied. The drug was confirmed to have a greater depressant action on the twitch contraction than on the fused tetanus of whole muscle. This was true also for single motor units. With tetanic stimulation the effect of dantrolene sodium was also dependent upon the motor unit type, fast or slow. A maximum depression of contractile tension occurred at a stimulation frequency of 64 Hz for fast EDL motor units whereas the maximum depression for ST slow units, the slowest units tested, was at a stimulation frequency of 14 Hz.

Anesthesia↗
PubMed1993

Effects of LY274614, a competitive NMDA receptor antagonist, on the micturition reflex in the urethane-anaesthetized rat.

1. The effects of 3 competitive N-methyl-D-aspartate (NMDA) receptor antagonists, LY274614, LY233536 and LY235723, on the micturition reflex and external urethral sphincter EMG activity, were examined either under isovolumetric conditions or during continuous filling cystometry in urethane-anaesthetized (1.2 g kg-1, s.c.) rats. 2. Intravenous administration of LY274614 (3-30 mg kg-1) inhibited in a dose-dependent fashion both bladder and sphincter activity in the intact rats. In addition, the volume threshold for inducing micturition was increased and voided volume was decreased. 3. Intrathecal administration of LY274614 (0.06-30 micrograms) similarly inhibited bladder and sphincter activity during cystometry in intact rats. 4. In chronic spinal cord (T6-T8) transected rats LY274614 (0.1-30 mg kg-1, i.v.) did not alter bladder activity under isovolumetric conditions but decreased the amplitude of micturition contractions and sphincter EMG activity during cystometry at a dose of 10-30 mg kg-1. 5. The inhibitory effects of i.v. administration of LY274614, on bladder and sphincter activity induced by infusion of chemical irritant (0.1% acetic acid) or saline, were similar; except that a slightly larger dose was needed to inhibit sphincter activity during acetic acid infusion. 6. Peak amplitude of micturition contractions recovered to 50% of control 3 h following i.v. (30 mg kg-1) or i.t. (6 micrograms) administration of LY274614. 7. Two other chemically related NMDA antagonists, LY233536 and LY235723 produced similar but less potent effects than LY274614 when given i.v. 8. These data indicate that glutamatergic transmitter mechanisms at the level of the spinal cord are important in modulating bladder activity in the intact animal, but that these mechanisms do not contribute to bladder reflexes in the chronic spinal rat. These mechanisms may, however, contribute to sphincter activity in both intact or chronic spinal rats.

Acetates↗
PubMed1995

Elevation of plasma noradrenaline levels in urethane-anaesthetized rats by activation of central prostanoid EP3 receptors.

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) and its receptor subtype ligands on plasma levels of catecholamines in urethane-anaesthetized rats. 2. Administration of PGE2 (0.15, 0.3 and 1.5 nmol per animal, i.c.v.) dose-dependently elevated plasma levels of noradrenaline (NA), while the levels of adrenaline were not affected. 3. Administration of sulprostone (EP3/EP1 agonist) and misoprostol (EP3/EP2 agonist) effectively elevated plasma NA levels in a dose-dependent manner (0.1, 0.3, and 1.0 nmol per animal). Butaprost (EP2 agonist) (0.3, 1.0 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega-trinor PGE2 (EP1/EP3 agonist) effectively elevated plasma NA levels only at its highest dose (1.0 nmol per animal), but this elevation was not attenuated by pretreatment with SC-19220 (selective EP1 antagonist) (20 nmol per animal, i.c.v.). 4. The potency of these test agents in elevating plasma levels of NA was as follows; misoprostol > sulprostone > PGE2 > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3-receptors induces central sympathetic outflow in rats.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Inhibition of vagally mediated gastric acid secretion by activation of central prostanoid EP3 receptors in urethane-anaesthetized rats.

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane. 2. Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EP1 receptor agonist) reduced vagally mediated gastric acid secretion in a dose-dependent manner (0.1, 0.3 and 1.0 nmol per animal). Butaprost (EP2 receptor agonist) (0.3 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega- trinor PGE2 (EP1/EP3 receptor agonist) attenuated vagally mediated gastric acid secretion only at its highest dose (1.0 nmol per animal); this antisecretory effect was not prevented by pretreatment with SC-19220 (selective EP1 receptor antagonist) (20 nmol per animal, i.c.v.). 3. The potency of these test agents in attenuation of vagally mediated gastric acid secretion was as follows: misoprostol > or = sulprostone > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3 receptors induces inhibition of vagally mediated gastric acid secretion in rats.

Anesthetics, Intravenous↗
PubMed1985

Intracisternal glycine activates the micturition reflex in urethane-anaesthetized rats.

Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.

Anesthesia↗
PubMed1968

The effects of chloralose-urethane and sodium pentobarbitone anaesthesia on the local and autonomic components of the circulatory response to arterial hypoxia.

1. The circulatory and respiratory responses to severe arterial hypoxia were studied in normal rabbits, ;de-efferented' rabbits without functioning autonomic effectors, and atropinized animals before anaesthesia and during chloralose-urethane and sodium pentobarbitone anaesthesia. Net systemic autonomic activity and autonomic activity to the heart was assessed from a comparison of the responses of the various preparations.2. In the normal spontaneously breathing animal each anaesthetic had a similar mode of action, and modified qualitatively the circulatory response present before anaesthesia. In the ;de-efferented' animal the circulatory response was determined by the local effects of hypoxia, and was altered only quantitatively during anaesthesia.3. In the normal unanaesthetized animal the reflex changes in autonomic activity during hypoxia consisted of a large increase in vagal efferent activity, a decrease in cardiac sympatho-adrenal activity, and an increase in total sympatho-adrenal constrictor activity.4 In hypoxia during anaesthesia the vagal efferent activity no longer increased, but the change in sympatho-adrenal activity to heart and systemic circulation was the same as before anaesthesia in the spontaneously breathing animal. During anaesthesia with controlled ventilation systemic sympatho-adrenal activity increased further, and bradycardia again developed. The bradycardia was now due exclusively to reduction in cardiac sympathetic activity and not to an increase in vagal efferent activity.

Animals↗
PubMed1982

Permeability of blood-retinal barriers in urethane-induced rat retinopathy: a fluorescein angiographic, vitreous fluorophotometric, and fluorescence microscopic study.

Urethane-induced rat retinopathy, characterised by permeability abnormalities of the blood-retinal barriers (BRB), was studied during the developmental phases by fluorescein fundus angiography (FFA), vitreous fluorophotometry (VF), and fluorescence microscopy (FM). A distinction based on VF values could be made at the p less than 0.02 confidence level between the retinopathic rats as a group and the control rats. Fluorescence microscopy provided a basis, however, for subdividing the test group into those rats with evidence of intraretinal leakage of NaFl and those without. Statistical analysis of the VF values of the control (A), nonleaky retinopathic (B), and leaky retinopathic (C) rats showed no significance between groups A and B, but highly significant differences between groups A and C (p less than 0.001) and between groups B and C (p less than 0.01). Fluorescence microscopy also showed that leakage of NaFl from retinal vessels occurred only after the retinopathy has progressed to the point where retinal vessels had become incorporated into the pigment epithelium. We conclude from this fluorescent marker clinicopathological study that breakdown of the blood-retinal barriers is a result of an interaction between the retinal pigment epithelium (RPE) and the retinal vessels after the vessels become incorporated into the RPE.

Animals↗
PubMedDate not supplied

Lack of norepinephrine--neuropeptide Y interactions in the hypothalamic control of cardiovascular regulation in urethane-anesthetized rats.

Noradrenergic input to the hypothalamus is implicated in cardiovascular and behavioral regulation. The hypothalamus also contains high concentrations of neuropeptide Y (NPY), which often is colocalized in noradrenergic neurons. Systemically, NPY has been demonstrated to act synergistically with norepinephrine. Injections of concentrated solutions of NPY into the cerebral ventricles or hypothalamus have been found to alter ingestive behaviours, but the role of NPY in cardiovascular regulation is unknown. The objectives of this study were to determine if NPY injected directly into the hypothalamus elicits cardiovascular responses and (or) if the simultaneous administration of NPY with norepinephrine alters the cardiovascular responses elicited by norepinephrine alone. The hypothalamus of the urethane-anesthetized rat was mapped for heart rate and blood pressure responses to injections of one of the following: saline; NPY (1.9 or 0.6 pmol per injection site); norepinephrine (24, 81, or 243 nmol per injection site); or the combination of norepinephrine plus NPY. Site and drug selection were randomized. Injections of 0.25 microL were at 1.0 microL/min, bilaterally for bilateral structures and unilaterally for midline structures. Norepinephrine routinely elicited dose-dependent increases in blood pressure with latencies of approximately 1 min, which peaked by 3-5 min, accompanied or followed by tachycardia. Saline and NPY injections alone elicited no significant responses in any site. When NPY was injected together with norepinephrine, there were no significant alterations in cardiovascular variables except for attenuation of pressor responses when NPY was injected into the preoptic region and attenuation of tachycardia when NPY was injected into the caudal hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1994

Effect of potassium-induced cortical spreading depression on prostaglandin-induced fever in conscious and urethane-anesthetized rats.

Potassium-induced cortical spreading depression (CSD) on prostaglandin E1 (PGE1) induced fever has been investigated in a dose-responsive experimental design in both conscious and urethane-anesthetized adult male Sprague-Dawley rats. While CSD in itself had no effect on nonfebrile body temperature even under cold ambient conditions, CSD significantly suppressed small but not large fevers induced by intracerebroventricular PGE1. The increased oxygen consumption during fever was also reduced. We also explored the possible involvement of the antipyretic peptide arginine vasopressin, in the CSD-induced suppression of fever. Long term castrated rats have significantly reduced ventral septal levels of this peptide, yet CSD was effective in suppressing the initial 40 min of PGE1 fever in these animals. Thus we conclude that increased release of ventral septal arginine vasopressin is probably not involved in the action of CSD on fever.

Anesthesia↗
PubMed1995

Strychnine-dependent allodynia in the urethane-anesthetized rat is segmentally distributed and prevented by intrathecal glycine and betaine.

The blockade of spinal glycine receptors with intrathecal strychnine produces a reversible allodynia-like state in the rat. Thus, hair deflection, in the presence of intrathecal strychnine, induces cardiovascular and motor withdrawal responses comparable with those evoked by noxious thermal, mechanical, or chemical stimulation in the absence of strychnine. In the present study, we mapped the cutaneous sites of abnormal sensitivity to hair deflection throughout the strychnine time course to investigate the segmental distribution of strychnine-induced allodynia. The ability of intrathecal glycine and the glycine derivative betaine to reverse strychnine-induced allodynia was also determined using dose-response analysis. Following intrathecal strychnine (40 micrograms), stroking the legs, flanks, lower back, and tail with a cotton-tipped applicator evoked a pronounced increase in mean arterial pressure, tachycardia, and an abrupt motor withdrawal response in urethane-anesthetized rats. These abnormal responses were only evoked by hair deflection at discrete sites, corresponding to the cutaneous dermatomes innervated by spinal segments near the site of strychnine injection. In rats with intrathecal catheters lying laterally in the subarachnoid space, allodynic sites were observed unilaterally on the ipsilateral side of intrathecal strychnine injection. Recovery from strychnine was complete by 30 min in all affected dermatomes. The cardiovascular and motor withdrawal responses to hair deflection were dose dependently inhibited by intrathecal glycine and intrathecal betaine. The ED50 (95% confidence interval) for intrathecal glycine was 609 (429-865) micrograms for the heart rate response, 694 (548-878) micrograms for the pressor response, and 549 (458-658) micrograms for the motor withdrawal response. The corresponding values for intrathecal betaine were 981 (509-1889), 1045 (740-1476), and 1083 (843-1391) micrograms, respectively. There was no difference in the effect of betaine on sensory-evoked cardiovascular and motor responses. Cortical electroencephalographic activity was not affected by intrathecal glycine or betaine, consistent with a spinal locus of action in reversing strychnine-induced allodynia. These results support the hypothesis that removal of spinal glycinergic modulation from low threshold afferent input with intrathecal strychnine results in segmentally localized, tactile-evoked allodynia.

Anesthetics, Intravenous↗