RESUMEN
Immunohistochemical study of rat mesenteric arteries showed dense innervation of adrenergic nerves, calcitonin gene-related peptide (CGRP)-containing nerves (CGRPergic nerves), nitric oxide-containing nerves (nitrergic nerves). Double-immunostaining revealed that most CGRPergic or nitrergic nerves were in close contact with adrenergic nerves. CGRPergic and transient receptor potential vanilloid-1 (TRPV1)-immunopositive nerves appeared in the same neurone. In rat perfused mesenteric vascular beds without endothelium and with active tone, perfusion of nicotine, or bolus injection of capsaicin and acetylcholine and periarterial nerve stimulation (PNS) lowered pH levels of out flowed perfusate concomitant with vasodilation. Cold-storage denervation of preparations abolished pH lowering induced by nicotine and PNS. Guanethidine inhibited PNS- and nicotine-, but not acetylcholine- and capsaicin-, induced pH lowering. Pharmacological analysis showed that protons were released not only from adrenergic nerves but also from CGRPergic nerves. A study using a fluorescent pH indicator demonstrated that nicotine, acetylcholine and capsaicin applied outside small mesenteric artery lowered perivascular pH levels, which were not observed in Ca(2+) free medium. Exogenously injected hydrochloric acid in denuded preparations induced pH lowering and vasodilation, which was inhibited by denervation, TRPV1 antagonists and capsaicin without affecting pH lowering. These results suggest that excitement of adrenergic nerves releases protons to activate TRPV1 in CGRPergic nerves and thereby induce vasodilation. It is also suggested that CGRPergic nerves release protons with exocytosis to facilitate neurotransmission via a positive feedback mechanism.
Asunto(s)
Arterias Mesentéricas/inervación , Mesenterio/irrigación sanguínea , Mesenterio/inervación , Comunicación Paracrina/fisiología , Vasodilatación/fisiología , Animales , Humanos , Arterias Mesentéricas/metabolismo , Mesenterio/metabolismoRESUMEN
BACKGROUND AND PURPOSE: A ketolide antibiotic, telithromycin, has side effects including temporary loss of consciousness in clinical use, but the underlying mechanisms remain unclear. This study investigated the effects of telithromycin on perivascular nerve function in rat mesenteric arteries, in comparison with those of macrolide (erythromycin and clarithromycin) and new quinolone antibiotics (levofloxacin and gatifloxacin). EXPERIMENTAL APPROACH: In vitro, vascular responses and release of noradrenaline induced by periarterial nerve stimulation (PNS) of rat perfused mesenteric vascular beds were measured in the presence of each antibiotic. In vivo blood pressure measurement was performed in Wistar rats. KEY RESULTS: In mesenteric preparations with resting tone, telithromycin (10 nM-10 microM) markedly inhibited PNS (4-12 Hz)-induced adrenergic nerve- and exogenous noradrenaline-mediated vasoconstriction, whereas the other antibiotics slightly inhibited PNS-induced responses without affecting noradrenaline-induced responses. Telithromycin significantly reduced PNS (12 Hz)-evoked noradrenaline release in the perfusate. In pre-constricted preparations with or without endothelium, telithromycin (0.1 nM-10 microM) caused a concentration-dependent vasodilation. Telithromycin (10 nM) inhibited calcium-induced vasoconstriction in high KCl and calcium-free medium. None of the antibiotics used affected PNS (0.5-2 Hz)-induced calcitonin gene-related peptide (CGRP) nerve- and exogenous CGRP-mediated vasodilation. Intravenous injection of telithromycin significantly lowered blood pressure in anaesthetized rats. CONCLUSIONS AND IMPLICATIONS: These results suggest that telithromycin causes not only strong inhibition of perivascular adrenergic neurotransmission but also a vasodilator action in mesenteric vascular beds and hypotension. It is thus possible that telithromycin increases visceral blood flow, consequently reducing cerebral blood flow and resulting in a temporary loss of consciousness.
Asunto(s)
Antibacterianos/farmacología , Cetólidos/farmacología , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/inervación , Transmisión Sináptica/efectos de los fármacos , Acetilcolina/farmacología , Animales , Péptido Relacionado con Gen de Calcitonina/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Endotelio Vascular/efectos de los fármacos , Masculino , Arterias Mesentéricas/fisiología , Norepinefrina/farmacología , Perfusión , Ratas , Ratas Wistar , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/metabolismo , Sistema Nervioso Entérico/fisiología , Arteria Mesentérica Superior/inervación , Regeneración Nerviosa/fisiología , Receptor de Angiotensina Tipo 2/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Western Blotting , Péptido Relacionado con Gen de Calcitonina/farmacología , Sistema Nervioso Entérico/citología , Ganglios Espinales/metabolismo , Imidazoles/farmacología , Losartán/farmacología , Arteria Mesentérica Superior/metabolismo , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/metabolismo , Factor de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Neuropéptido Y/metabolismo , Norepinefrina/farmacología , Fenol , Piridinas/farmacología , Ratas , Ratas Wistar , Soluciones Esclerosantes , Resistencia Vascular/fisiología , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , Vasoconstrictores/farmacologíaRESUMEN
Our previous report showed that innervation of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-containing nerves in rat mesenteric resistance arteries was markedly reduced by topical application of phenol, and that nerve growth factor (NGF) facilitates the reinnervation of both nerves. We also demonstrated that a CGRP superfamily peptide, adrenomedullin, is distributed in perivascular nerves of rat mesenteric resistance arteries. In the present study, we investigated the influence of adrenomedullin on the reinnervation of mesenteric perivascular nerves following topical phenol treatment. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the third branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 7. Topical phenol treatment caused marked reduction of the density of NPY-like immunoreactive (LI)- and CGRP-LI nerve fibers in the arteries. Adrenomedullin (360 or 1000 ng/h) or NGF (250 ng/h), which was administered intraperitoneally for 7 days using an osmotic mini-pump immediately after topical phenol treatment, significantly increased the density of CGRP-LI- and NPY-LI nerve fibers compared with saline. Treatment with adrenomedullin (1000 ng/h) or NGF restored adrenergic nerve-mediated vasoconstriction and CGRP nerve-mediated vasodilation in the perfused mesenteric artery treated topically with phenol. These results suggest that adrenomedullin, like NGF, has a facilitatory effect on the reinnervation of perivascular nerves.
Asunto(s)
Adrenomedulina/administración & dosificación , Arterias Mesentéricas/efectos de los fármacos , Fibras Nerviosas/efectos de los fármacos , Fenoles/farmacología , Vasodilatadores/administración & dosificación , Análisis de Varianza , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Estimulación Eléctrica/métodos , Inmunohistoquímica/métodos , Arterias Mesentéricas/inervación , Fibras Nerviosas/metabolismo , Factor de Crecimiento Nervioso/administración & dosificación , Neuropéptido Y/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Vasodilatación/efectos de los fármacosRESUMEN
We have previously shown that age-related reduction of innervation and function in mesenteric perivascular calcitonin gene-related peptide-containing vasodilator nerves takes place in spontaneously hypertensive rats. The present study was performed to investigate innervation and functional changes in perivascular calcitonin gene-related peptide- and adrenergic neuropeptide Y-containing nerves after topical treatment with phenol, which damages nerve fibers, around the rat superior mesenteric artery. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) or saline (sham rats) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the 3rd branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 3 through day 14. The innervation levels of calcitonin gene-related peptide-like immunoreactivity containing fibers and neuropeptide Y-like immunoreactivity containing fibers were markedly reduced on day 3 to day 14 and on day 5 to day 14 after the treatment, compared with those in sham-operated rats, respectively. In perfused mesenteric vascular beds isolated from phenol-treated rats, adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide nerve-mediated vasodilation in response to periarterial nerve stimulation (2-12 Hz) were significantly decreased on day 3 and day 7. Neurogenic release of norepinephrine in phenol-treated rats on day 7 was significantly smaller that that in sham-operated rats. Nerve growth factor content in the mesenteric arteries of phenol-treated rats was significantly lower than that in sham-operated rats. Administration of nerve growth factor using osmotic mini-pumps for 7 days after the phenol treatment resulted in greater density of calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity fibers than in phenol-treated rats and restored decreased vascular responses to periarterial nerve stimulation. These results suggest that topical phenol-treatment of the mesenteric artery effectively induces functional denervation of perivascular nerves, which can be prevented or reversed by nerve growth factor treatment.
Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/metabolismo , Arterias Mesentéricas/inervación , Fibras Nerviosas/efectos de los fármacos , Neuropéptido Y/metabolismo , Fenol/administración & dosificación , Administración Tópica , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunohistoquímica/métodos , Fibras Nerviosas/metabolismo , Factor de Crecimiento Nervioso/administración & dosificación , Norepinefrina/farmacología , Ratas , Ratas Wistar , Factores de Tiempo , Vasoconstricción/efectos de los fármacosRESUMEN
Distribution of adrenomedullin (AM)-containing perivascular nerve fibers was studied in rat mesenteric arteries. Many fibers containing AM-like immunoreactivity (LI) were observed in the adventitia. AM-LI fibers were abolished by cold storage denervation or capsaicin but not 6-hydroxydopamine. Double immunostainings showed colocalization of AM-LI with calcitonin gene-related peptide (CGRP)-LI. The dorsal root ganglia had many AM-positive cells and AM mRNA detected by RT-PCR. Electron microscopy study revealed high proportions of immunogold labeling for AM and colocalization of both AM-LI and CGRP-LI in unmyelinated nerve axons. These results suggest that AM-containing perivascular nerves are distributed in the rat mesenteric artery.
Asunto(s)
Axones/ultraestructura , Péptido Relacionado con Gen de Calcitonina , Ganglios Espinales/ultraestructura , Arterias Mesentéricas/inervación , Péptidos , Adrenomedulina , Animales , Axones/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Tejido Conectivo/inervación , Ganglios Espinales/metabolismo , Masculino , Microscopía Electrónica , Péptidos/metabolismo , Ratas , Ratas WistarRESUMEN
1. beta-Adrenoceptor blocking activities of nipradilol, its four optical isomers (RR, RS, SR, SS) and denitro nipradilol were evaluated using pig isolated coronary arteries. 2. (-)-Isoprenaline produced concentration-dependent relaxations of the arteries, which were antagonized by nipradilol, its four optical isomers or denitro nipradilol under KCl-induced contracture. 3. The order of pA2 values for beta-adrenoceptor blocking activities was SR > nipradilol > SS > or = denitro nipradilol > RR > RS. 4. The nitroxy group in nipradilol appears to enhance its beta-adrenoceptor blocking activity, because the beta-adrenoceptor blocking activity of nipradilol was more potent than that of denitro nipradilol. 5. Isomers that have the S configuration (SR, SS) at the 2' position (having a hydroxyl group) in the aryloxypropanolamine showed more potent beta-adrenoceptor blocking activity than isomers that have the R configuration (RR, RS). 6. Isomers that have the R configuration (SR, RR) at the 3 position (having a nitroxy group) in the benzopyran ring showed more potent beta-adrenoceptor blocking activity than those with the S configuration (SS, RS). 7. It is suggested that the difference in configuration of the chemical structure of nipradilol may result in variations of binding affinity for the beta-adrenoceptor.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Vasos Coronarios/efectos de los fármacos , Propanolaminas/farmacología , Receptores Adrenérgicos beta/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/química , Animales , Vasos Coronarios/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Isomerismo , Isoproterenol/farmacología , Masculino , Propanolaminas/química , Receptores Adrenérgicos beta/fisiología , Relación Estructura-Actividad , Porcinos , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
We studied the use of high-performance liquid chromatography (HPLC) with spectrofluorometric detection, using a solid-phase extraction for a simple, rapid and sensitive determination of plasma carvedilol levels in rats. Extracted aliquots were analyzed by HPLC, using a reversed-phase octadecyl silica column. The analytical mean recovery of carvedilol added to the blank plasma was 94.2%. The detection limit was 3.6 ng/ml in the plasma. The reproducibilities (C.V.) were 2.7-7.5% for the within-day assay, and 2.6-7.4% for the between-day assay, indicating that the method was effective for the determination of carvedilol plasma levels.
Asunto(s)
Carbazoles/sangre , Cromatografía Líquida de Alta Presión/métodos , Propanolaminas/sangre , Vasodilatadores/sangre , Animales , Calibración , Carbazoles/análisis , Carvedilol , Cuello del Útero/metabolismo , Femenino , Masculino , Propanolaminas/análisis , Control de Calidad , Ratas , Ratas Sprague-Dawley , Cola (estructura animal)/metabolismo , Factores de Tiempo , Vasodilatadores/análisisRESUMEN
We studied the use of high-performance liquid chromatography (HPLC) with a spectroflurometric detector, using a solid-phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of plasma fleroxacin (FLRX) levels in rats. Extracted aliquots were analyzed by HPLC, using a reverse phase octadecyl silica column. The analytical mean recovery of FLRX added to the blank plasma averaged 101.4%. The detection limit was 58 ng/ml in the plasma. The reproducibilities (C.V.) were 0.50-3.22% in the within-day assay and 2.87 C.V.% in the between-day assay, indicating that the analysis method was effective in the determination of FLRX plasma levels.
Asunto(s)
Antiinfecciosos/sangre , Cromatografía Líquida de Alta Presión/métodos , Fleroxacino/sangre , Administración Oral , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacocinética , Ritmo Circadiano , Fleroxacino/administración & dosificación , Fleroxacino/farmacocinética , Masculino , Concentración Osmolar , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Dióxido de Silicio/química , Factores de TiempoRESUMEN
When pyrroloquinoline quinone (PQQ) was intraperitoneally injected into rats daily for 4 days at a dose of 11.5 mg/kg body weight/injection, functional and morphologic changes of the kidneys were clearly observed. The most prominent finding was necrotic and degenerative changes of the proximal tubular epithelium as well as hematuria and an elevation of serum creatinine concentration.
Asunto(s)
Riñón/efectos de los fármacos , Quinolonas/toxicidad , Animales , Creatinina/sangre , Riñón/patología , Riñón/fisiopatología , Masculino , Cofactor PQQ , Ratas , Ratas EndogámicasRESUMEN
A rise in blood and liver acetaldehyde concentrations following an intragastric administration of ethanol to rats was significantly inhibited when the quinone derivatives 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone (ubidecarenone, coenzyme Q10), 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid (pyrroloquinoline quinone, PQQ) and 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) were injected intraperitoneally, prior to ethanol load, at a dose of 10, 11.5 and 30 mg/kg of body weight, respectively. When acetaldehyde was incubated in vitro with 1,4-benzoquinone (3.7-13.0 mM) or PQQ (1.4-4.9 mM) at 0 and 40 degrees C, the acetaldehyde concentrations slowly decreased with incubation time at 40 degrees C. The results suggest that low acetaldehyde concentrations following ethanol load are due to an accelerated oxidation of acetaldehyde by PQQ in the liver and the circulating blood.
Asunto(s)
Acetaldehído/metabolismo , Benzoquinonas , Etanol/metabolismo , Quinonas/farmacología , Acetaldehído/sangre , Animales , Coenzimas , Etanol/administración & dosificación , Etanol/sangre , Técnicas In Vitro , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Cofactor PQQ , Quinolonas/metabolismo , Quinolonas/farmacología , Ratas , Ratas Endogámicas , Ubiquinona/análogos & derivados , Ubiquinona/farmacologíaAsunto(s)
Intoxicación por Tetracloruro de Carbono/fisiopatología , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Administración por Inhalación , Animales , Enfermedad Crónica , Hígado/patología , Hígado/fisiopatología , Circulación Hepática , Masculino , Ratas , Ratas EndogámicasAsunto(s)
Acetaldehído/metabolismo , Etanol/metabolismo , Hígado/metabolismo , Acetaldehído/administración & dosificación , Acetaldehído/sangre , Administración por Inhalación , Aerosoles , Animales , Etanol/administración & dosificación , Inyecciones Intravenosas , Masculino , Oxidación-Reducción , Ratas , Ratas EndogámicasRESUMEN
D-Pantethine-related metabolites, such as taurine, D-pantetheine, coenzyme A and D-pantothenate, activated yeast aldehyde dehydrogenase in vitro. D-Pantethine and cysteamine hydrochloride, however, strongly inhibited the activity of this enzyme.
Asunto(s)
Aldehído Deshidrogenasa/metabolismo , Panteteína/farmacología , Saccharomyces cerevisiae/enzimología , Compuestos de Sulfhidrilo/farmacología , Acetilcoenzima A/farmacología , Aldehído Deshidrogenasa/antagonistas & inhibidores , Coenzima A/farmacología , Cisteamina/farmacología , Activación Enzimática , Panteteína/análogos & derivados , Ácido Pantoténico/farmacología , Taurina/farmacologíaRESUMEN
Sake, a rice wine, induced hepatic collagen accumulation in rats. This was noted after 16 weeks of a liquid diet containing 35% ethanol by caloric content. However, under similar experimental conditions, whiskey and ethanol did not produce any changes. Hepatic collagenase activities in sake-fed rats were slightly, but significantly, higher than in the whiskey group. The central and pericellular liver fibrosis in sake-fed rats was caused possibly by either accelerated collagen synthesis or maturation, exceeding the increased collagen degradation. Mechanisms of enhanced fibrogenesis in sake-fed rats were discussed.
Asunto(s)
Bebidas Alcohólicas/toxicidad , Colágeno/metabolismo , Hígado/metabolismo , Acetaldehído/sangre , Alanina Transaminasa/sangre , Animales , Etanol/sangre , Etanol/toxicidad , Hígado/enzimología , Hígado/patología , Cirrosis Hepática Alcohólica/etiología , Cirrosis Hepática Alcohólica/metabolismo , Masculino , Colagenasa Microbiana/metabolismo , Mitocondrias Hepáticas/enzimología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.
Asunto(s)
Acetaldehído/metabolismo , Etanol/farmacología , Hígado/metabolismo , Taurina/farmacología , Acetaldehído/sangre , Alcoholismo/metabolismo , Aldehído Deshidrogenasa/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Etanol/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Taurina/sangre , Taurina/metabolismoRESUMEN
A rise in blood acetaldehyde concentrations following alcohol ingestion was significantly inhibited when healthy nonflushing subjects were administered a clinical dose of pantethine orally. However, similar findings were not observed in flushing (alcohol-sensitive) subjects lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment. Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of low Km ALDH by pantethine-related metabolites formed in the liver.
Asunto(s)
Acetaldehído/sangre , Intoxicación Alcohólica/tratamiento farmacológico , Rubor/fisiopatología , Panteteína/uso terapéutico , Compuestos de Sulfhidrilo/uso terapéutico , Adulto , Intoxicación Alcohólica/metabolismo , Animales , Etanol/sangre , Humanos , Hígado/análisis , Masculino , Panteteína/análogos & derivados , Ratas , Ratas EndogámicasAsunto(s)
Acetaldehído/metabolismo , Aldehído Deshidrogenasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Etanol/metabolismo , Regeneración Hepática , Masculino , Mitocondrias Hepáticas/enzimología , Ratas , Ratas EndogámicasRESUMEN
Blood ethanol levels following intravenous ethanol administration were much higher during anesthesia with diethyl ether (ether), phenobarbital and pentobarbital than in unanesthetized control rats. Blood acetaldehyde levels were significantly lower during anesthesia with ether. Ether inhibited alcohol dehydrogenase (ADH) activities in vitro in an uncompetitive fashion; Ki, ether concentration which produced 50% inhibition of NADH formation, was 9.7 mM. Pentobarbital produced slight elevations of ADH activities in vitro and phenobarbital had no effects. Acetaldehyde levels during anesthesia with phenobarbital and pentobarbital were slightly higher than in unanesthetized animals. Phenobarbital and pentobarbital inhibited aldehyde dehydrogenase (ALDH) activities in vitro in a noncompetitive fashion; Ki were 29 and 37 mM, respectively. Ether did not influence ALDH activities in vitro. Thus, pentobarbital was suggested as the most appropriate anesthetic agent in such animal experiments.