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PubMed1989

Effects of althesin and urethan-chloralose on neurohumoral cardiovascular regulation.

The cardiovascular effects of althesin (ALT) and urethan-chloralose (UC) anesthesia were compared in conscious, chronically instrumented rats. Althesin had no effect on arterial pressure or base-line resistance in the renal, superior mesenteric, and hindquarters vasculatures but increased heart rate. In contrast, UC decreased arterial pressure, heart rate, and mesenteric resistance. Although UC attenuated depressor responses to nitroglycerin, neither anesthetic significantly altered regional vascular reactivity to intravenous phenylephrine and nitroglycerin. The cardiac chronotropic baroreflex was examined by comparing the slope of the curves relating maximal changes (delta) in heart rate (pulse interval) that occurred at the point coinciding in time with the maximal changes in mean arterial pressure produced by phenylephrine and nitroglycerin. Neither anesthetic significantly altered the baroreflex slope (delta pulse interval/delta mean arterial pressure) for pressor and depressor stimuli. Both anesthetics attenuated the sympathoexcitatory response to cerebroventricular angiotensin II, although ALT had less of a depressive effect (pressor response during ALT and UC = 65 and 30%, respectively, of conscious). Plasma renin activity (PRA) and the hemodynamic response to peripheral angiotensin-receptor antagonism were significantly increased (PRA by almost 6-fold) during UC, whereas ALT was without effect. Similarly, UC but not ALT induced vasopressin-dependent vascular tone. Ganglionic blockade indicated that peripheral neurogenic tone was not altered by ALT anesthesia. These data suggest that althesin produces fewer hemodynamic disturbances than urethan-chloralose and largely maintains cardiovascular regulation intact.

Alfaxalone Alfadolone Mixture↗
PubMed2004

Strain differences in murine ventilatory behavior persist after urethane anesthesia.

Differences in breathing pattern between awake C57BL/6J (B6) and A/J mice are such that A/J mice breathe slower, deeper, and with greater variability than B6. We theorized that urethane anesthesia, by affecting cortical and subcortical function, would test the hypothesis that strain differences require a fully functional neuroaxis. We anesthetized B6 and A/J mice with urethane, placed them in a whole-body plethysmograph, and measured the durations of inspiration and expiration, respiratory frequency (Fr), and peak amplitude during exposure to room air (21% O2), hyperoxia (5 min, 100% O2), hypoxia (5 min, 8% O2), and posthypoxic reoxygenation (5 min, 100% O2). Breathing variability was assessed by calculating the coefficient of variation (CV) and by applying spatial statistics to Poincaré plots constructed from the timing and amplitude data. Even though Fr in anesthetized B6 and A/J mice was greater than that for unanesthetized animals, anesthetized A/J mice still breathed slower, deeper, and with greater variability than B6 mice at rest and during hyperoxia. During the fourth minute of hypoxia, Fr and its CV were not significantly different between strains. Even though Fr was similar between strains immediately after hypoxia, its CV was significantly greater for B6 than A/J mice. Posthypoxic Fr was significantly less than baseline Fr in B6 but not A/J mice, and the CV for posthypoxic Fr was greater for B6 but less for AJ mice compared with baseline CV. This difference in patterning was confirmed by spatial statistical analysis. We conclude that strain-specific differences in respiratory pattern and its variability are robust genetic traits. The neural substrate for these differences, at least partially, exists within subcortical structures generating the breathing pattern.

Anesthetics, Intravenous↗
PubMed1991

Influence of pentobarbital and urethane on release from magnocellular neurons.

We examined the responses of vasopressin-neurons (VP-neurons) and oxytocin-neurons (OT-neurons) to acute salt-loading in a group of conscious rats (CON, n = 8) and rats under sodium pentobarbital (NEM, 50 mg/kg, i.p., n = 8) or urethane (URE, 1.6 g/kg, i.p. n = 8) anesthesia. Fifteen minutes following the induction of anesthesia, sodium pentobarbital produced an increase in basal plasma osmolality (Posm, 290 +/- 2 to 296 +/- 3 mosm/kg H2O, p less than 0.007) while urethane did not change basal Posm (287 +/- 2 to 289 +/- 2 mosm/kg H2O). Neither anesthetic agent resulted in any significant changes in basal plasma levels of vasopressin-associated neurophysin (VP-RNP) and oxytocin-associated neurophysin (OT-RNP). In response to intravenous infusion of 18% saline, all three groups of rats had similar rises in Posm. The slopes of the relationship between the rise in plasma VP-RNP and the rise in Posm were markedly reduced in both groups of anesthetized animals compared to that observed for conscious animals (CON = 2.54 +/- 0.5; NEM = 1.22 +/- 0.18; URE = 1.17 +/- 0.24 fmol.ml-1.mosm-1.kg H2O-1 p less than 0.0126). The slopes of the relationship between the rise in plasma OT-RNP and the rise in Posm were not significantly (p less than 0.4478) different between the CON group and the NEM group, while the slope for the URE group was significantly (p less than 0.05) smaller than that for the CON group (CON = 10.9 +/- 1.5; NEM = 9.3 +/- 1.5; URE = 6.3 +/- 0.7 fmol.ml-1.mosm-1.kg H2O-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1980

Acute effects of arginine vasotocin on plasma and pituitary levels of prolactin in the male rat: influence of urethane anesthesia.

The acute effects of arginine vasotocin (AVT), a putative pineal peptide, on plasma levels of prolactin were investigated in the unanesthetized, estrogen-progesterone-treated male rat. A 10-microgram s.c. injection resulted in significantly increased levels of prolactin while a 1-microgram injection depressed plasma levels of this hormone; an inhibition of release was further suggested by increased levels of pituitary prolactin in rats treated with the lower dose. The same dose administered subcutaneously to urethane-anesthetized rats had no significant effect on plasma prolactin titers while a 10-microgram dose was still stimulatory. In anesthetized rats, no dose of the AVT administered (1 ng to 10 micrograms, s.c., or 1 fg to 1 microgram, i.v.) resulted in inhibition of prolactin release. In the unanesthetized normal male rat, 5 micrograms AVT first increased and then decreased levels of prolactin. Urethane anesthesia appears to mask an inhibitory effect of AVT on plasma prolactin levels in these animal preparations. Since AVT is capable of decreasing plasma prolactin levels, this peptide might be involved in the depression of plasma prolactin levels which appears to (at least partially) mediate pineal-induced gonadal degeneration.

Anesthesia↗
PubMed1996

Role of prostaglandins and calcitonin gene-related peptide in central vagal cholinergic-dependent protection against gastric injury in urethane-anesthetized rats.

The influence of central vagal activation induced by the thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally on gastric mucosal injury produced by 60% ethanol (4 ml.kg-1) was investigated in urethane-anesthetized rats. RX 77368 (3, 10 and 30 ng) inhibits dose dependently macroscopic gastric damage induced by intragastric administration of 60% ethanol by 18, 43 and 77%, respectively. The cytoprotective effect of intracisternal RX 77368 (30 ng) was completely blocked by cervical vagotomy, atropine (2 mg.kg-1 s.c.), and CGRP8-37 (100 micrograms.kg-1 i.v.) and partially inhibited by indomethacin (5 mg.kg-1 i.p.). Vagotomy, atropine, indomethacin and CGRP8-37 alone did not modify gastric mucosal lesions induced by ethanol in rats injected intracisternally with saline. The present data show that intracisternal injection of TRH analog in urethane-anesthetized rats protects against ethanol-induced gastric injury through vagal cholinergic dependent pathways which recruit prostaglandins and CGRP mechanisms.

Anesthesia↗
PubMed1996

Diminished expression of CYP1A1 in urethane-induced lung tumors in strain A/J mice: analysis by in situ hybridization and immunohistochemical methods.

We have investigated the regulation and expression of CYP1A1 in solid and papillary lung tumors induced by the carcinogen urethane. Female strain A/J mice were administered urethane (1 mg/g body wt) intraperitoneally, and when lung tumors were established at 16 weeks, mice were treated with 3-methylcholanthrene to induce CYP1A1. CYP1A1 mRNA was detected by in situ hybridization with a 3H-labeled RNA probe and quantitated by image analysis, whereas CYP1A1 protein was detected by immunohistochemical staining with an avidin-biotin complex procedure. Our results showed that in untreated control and tumor-bearing mice, the CYP1A1 mRNA was present at low levels, but the CYP1A1 protein was not detectable. Treatment with 3-methylcholanthrene induced increased levels of both CYP1A1 mRNA and protein in lung parenchyma and tumor foci. This induction was markedly higher in the parenchyma of control and tumor-bearing lungs than in either solid or papillary tumors. Differences in CYP1A1 mRNA and protein expression were not evident in solid and papillary tumors. In the parenchyma, induced CYP1A1 mRNA and protein were localized in the endothelial and alveolar septal cells. Endothelial cells in tumors also contained substantial CYP1A1 mRNA and protein, whereas low levels of both were found in lung tumor cells. Our finding of significant reduction in inducibility of CYP1A1 protein in conjunction with reduced CYP1A1 mRNA in tumor foci suggests reduced transcriptional activation as a regulatory mechanism. The lack of association between diminished CYP1A1 expression and either the tumor type or the mechanism mediating metabolic activation supports the hypothesis that the persistence of lung tumors may be due, in part, to a restricted capability for the formation of reactive intermediates.

Animals↗
PubMedDate not supplied

Lymphocyte functions in the rat spleen at various times after urethan administration.

The effect of urethan on various spleen-lymphocyte functions was studied in the rat for 45 days after administration of the carcinogen. For 3 days following the last injection of urethan, the total cell number and LPS reactivity were greatly reduced. Certain reactivities, probably T-cell dependent functions, such as responsiveness to the in vitro mitogenic effect of PHA, Con A, and primary stimulation by histocompatibility alloantigens in the one-way reaction, were selectively enriched during the first 2 days. Thereafter several dissociations of these lymphocyte functions can be observed: i.e., various intervals succeed during which one function may be enriched and other(s) diminished. It seems that the kinetics of enrichment, decay and recovery of the T-cell subsets involved in the reactions investigated follow a distinctive profile for each one of them. It is suggested, as a working hypothesis, that the unbalanced situations derived from the time-course discordance of the quantitative changes in the various lymphocyte functions may allow, or even enhance, tumor development.

Animals↗
PubMed1983

Different susceptibility of BALB/Mo and BALB/c mice to cytogenetic damage induced by urethan.

The urethan-induced clastogenic effect in BALB/Mo mice carrying the Moloney murine leukemia virus (M-MuLV) as an endogenous retrovirus was evaluated by short-term micronucleus assay on bone marrow polychromatic erythrocytes (PCE). A single urethan injection in 3 dose levels brought the incidence of micronucleated PCE far above baseline values when scoring was performed 24 h after treatment; this increase was higher in BALB/Mo than in M-MuLV-free BALB/c mice. In a second experiment, micronucleated PCE incidence was determined as a function of the time interval after a single injection of 1 mg urethan/g of body weight. Higher values of micronucleated PCE were scored in BALB/Mo than in BALB/c mice; statistically significant differences were found at 24 and 48 h after treatment.

Animals↗
PubMed1994

Influence of urethane anesthesia and abdominal surgery on gastrointestinal motility in rats.

The influence of various experimental treatments on propulsive gastrointestinal motility was examined in rats, using inulin as a marker. In unanesthetized rats without any surgery, the distribution center of inulin, which was expressed as a dimensionless distance normalized by the length of the small intestine, reached 0.587 down the intestinal tract from the pylorus 60 min after the intragastric administration of inulin. However, the distribution center of inulin moved only 0.061 in 60 min in unanesthetized rats with minimial abdominal surgery for intraduodenal administration of inulin, and did not move in unanesthetized rats with cannulas for perfusion or in the rats anesthetized with urethane and treated with abdominal surgery. In urethane-anesthetized rats without surgery, almost 100% of the inulin was recovered from the stomach 60 min after intragastric administration. These results suggest that gastrointestinal motility is extensively suppressed by minimal abdominal surgery as well as by anesthesia.

Abdomen↗
PubMed1993

Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats.

Chloral hydrate, pentobarbitone and urethane were evaluated and compared for onset, duration and depth of anaesthesia, cardiovascular and respiratory effects, nociception and mortality in adult male rats. Chloral hydrate (300 and 400 mg/kg) severely depressed the cardiovascular and respiratory systems. Duration of anaesthesia was linearly related to dose, and anaesthetic depth and analgesia were excellent. Pentobarbital (40 mg/kg) produced a short period of light surgical anaesthesia. Moderate to severe respiratory and cardiovascular depression occurred. Duration of anaesthesia was not related to dose. Urethane (1.2 and 1.5 g/kg) caused moderate cardiovascular depression. In addition, mortality was high at the 1.5 g/kg dose. Duration of anaesthesia was greater than 24 h for most animals. Anaesthesia depth and analgesia were excellent.

Anesthesia↗
PubMedDate not supplied

Validation of the mouse peripheral blood micronucleus assay using acridine orange supravital staining with urethane.

The mouse peripheral blood micronucleus assay using acridine orange supravital staining was compared with the standard bone marrow assay using urethane (ethyl carbamate)-treated mice. Urethane was intraperitoneally injected to CD-1 and BDF1 mice at doses ranging from 62 to 1000 and 62 to 250 mg/kg, respectively. Peripheral blood was collected from the tail 0, 24, 48, and 72 h and bone marrow cells were smeared at 24 and 42 h after the treatment. Although the response of micronucleus induction in peripheral reticulocytes was delayed by about 24 h compared to that in bone marrow polychromatic erythrocytes, the maximum frequencies of micronucleated young erythrocytes were comparable. Therefore, the peripheral blood micronucleus assay using the acridine orange supravital staining method may provide a good alternative to the conventional bone marrow assay.

Acridine Orange↗
PubMed1978

[Effect of urethane on the granulopexic activity of the reticuloendothelial system and the production of virus inhibiting factor or interferon].

Urethane (ethyl carbamate) did not affect the rate of the clearance of carbon from the blood in splenectomized mice, while this compound slowed down the carbon clearance in intact mice. Production of virus-inhibiting factor (IF) or interferon, especially early IF induced by virus was impaired by urethane in splenctomized mice as well as intact ones. The role of reticulo-endothelial system in IF formation was discussed.

Animals↗
PubMed1975

Evaluation of irradiation-plus-urethan-induced murine leukemia virus "release" using a new method for quantitation of oncornaviruses in tissues.

The quantity of C-type RNA tumor viruses in homogenate-sonicates of thymus-bone marrow tissues of C57BL/6J and RFM/Un mice 10 days after irradiation (X-rays or gamma-rays)-plus-urethan treatments is no greater than that in thymus-bone marrow homogenates from nontreated control mice. These results indicate that the leukemogenic activity, shown to be present in such thymus-bone marrow homogenates at this time after irradiation-plus-urethan treatment, is not due to change in quantity of C-type viruses as has been proposed. Virus quantity in tissues was evaluated by a new procedure that includes use of a microchamber with the sides situated on rotor radii so as to produce a uniform virus-containing sediment of tissue homogenate-sonicate that is evaluated by electron microscopic examination of this sections cut perpendicular to the membrane surface. Samples containing as little as 105 to 106 viruses can be relatively easily counted. Semipurified or purified viruses can also be counted after mixing with a tissue homogenate-bovine serum albumin diluent.

Animals↗
PubMedDate not supplied

Urethane-induced hyperglycemia in rats.

The occurrence of hyperglycemia and glucosuria was investigated in urethane anesthetized rats. The substance found in urine was chromatographically identified with d-glucose. Marked increase in the arterial blood catecholamine concentration was observed. Hyperglycemia appeared after infusion of catecholamines in concentration comparable to that found in the blood of anaesthetized rats. The results support a hypothesis that the urethane-induced hyperglycemia is caused by an endogenous adrenaline liberation. Some observations in hypophysectomized and adrenalectomized rats indicate that the adrenal steroids may play a role in this reaction.

Adrenalectomy↗
PubMed1989

The changes of glycosaminoglycan in the growth of urethane-induced mouse mammary tumors.

The changes of glycosaminoglycan (GAG) in the growth of urethane-induced mammary tumors in BALB/c mice were investigated. The artificial mammary tumor was chemically induced by urethane. Successive homo-transplantations of this artificial mammary tumor were successfully achieved at the rate of 100%. Histologically, this artificially induced transplantable mammary tumor (MC) line maintained the characteristics of adenoacanthoma of primary tumors in each successive generation. MC in each generation showed a logarithmic growth beginning from about the 5th day after transplantation, and their growth became slow about the 30th day. Histochemically, GAG components in MC were distributed into the interstitial tissue and into some of the squamous metaplastic epithelial cell layers. Biochemically, GAG components consisted primarily of hyaluronic acid (HA), dermatan sulfate (DS) and chondroitin sulfate (ChS), but there were also small amounts of components which could not be identified. The HA content of MC increased during the logarithmic growth phase and decreased during the stationary phase. However, DS and ChS contents increased during the stationary phase of MC. These increases, histologically, corresponded with propagations in fibrous interstitial tissue. In the final analysis, it is surmised that HA is involved in the take and growth of MC (adenoacanthoma) in mice, while DS and/or ChS are involved in the proliferation of the fibrous interstitial tissue cells of the tumor.

Adenocarcinoma↗
PubMed1988

Perforant path activation of the hippocampus: spatial distribution, effects of urethane and atropine.

Spatial distribution of field responses evoked by perforant path stimulation were studied in the hippocampus of both anaesthetized and drug-free rats. Simultaneous recordings with an array of 4 electrodes allowed us to construct a 2-dimensional map of the evoked field potentials. In addition, we examined the effects of atropine-SO4 and urethane on the amplitude of the dentate response. Trisynaptic activation of the CA1 region occurred regularly in the drug-free rat while CA1 population spikes were rarely seen in the anaesthetized animal. The latency of the CA1 population spike was shortest at the fimbrial side and increased gradually towards the subicular side. In the dentate gyrus atropine increased the amplitude of the population spike. We suggest that atropine may interfere with the septo-hippocampal feed-forward inhibition, and urethane may decrease the effectiveness of the perforant path-granule cell synapse, as well as the intrahippocampal excitatory circuit.

Animals↗
PubMed1986

[Kinetics of DNA reparative replication in the spleen cells of CBA- and C57BL/6-strain mice induced by urethane and and the influenza virus].

Different kinetics of DNA repair replication induced by urethan and influenza virus was detected in mice of varying genotypes. Inhibition of repair replication was detected in the lymphocytes of C57BL/6 mice, infected with influenza virus and treated with urethan. No inhibition of repair replication was noted in CBA mice which is characteristic of resistance to influenza virus. However, stimulation of repair replication by influenza virus was observed in these cells.

Animals↗
PubMed1985

The H-2 complex affects the frequency of urethan-induced chromosomal aberrations.

We have already found that H-2 complex has an apparent effect on the development of lung tumors in mice. In connection with this finding, the incidence of in vivo urethan-induced chromosomal aberrations of bone marrow cells was examined in H-2 congenic strains. These strains could be divided into two groups, one with a higher frequency of chromosomal aberrations such as A.AL (H-2a1), A.TL (H-2t1), B10.A (H-2a) and B10.S (9R) (H-2t4), and the other with a lower incidence such as B10 (H-2b), A.SW (H-2s), B10.S (H-2s) and B10.S(7R) (H-2t2). These results suggested that a putative gene mapped to the chromosomal segment between E beta and D may affect the incidence of urethan-induced chromosomal aberrations.

Animals↗