Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Halothane”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed1988

Halothane induced vasomotion of coronary, renal and iliac arterial rings in malignant hyperthermia susceptible swine.

Animals were identified as porcine malignant hyperthermia susceptible by halothane testing and were slaughtered at 90 kg of body weight. Coronary, renal and iliac arteries were isolated, dissected and 5 mm rings were mounted in 20 mL organ baths with modified Krebs solution maintained at 37 degrees C and oxygenated with 95% O2, 5% CO2. Halothane at 0%, 0.5%, 2% and 5% concentration was bubbled in the organ baths and mechanical responses were recorded over a period of 25 min. Halothane free arteries remained quiescent and the arteries from the halothane sensitive and from the halothane resistant groups reacted similarly. All arteries in the presence of halothane responded with an initial contraction of short duration followed by a relaxation and both phenomena occurred in a concentration-dependent fashion. The iliac artery was the most sensitive to halothane and responded to 0.5% concentration while coronary and renal arteries maintained the resting tension of 4 g. These results demonstrate that vascular smooth muscle, like skeletal muscle and unlike respiratory smooth muscle, has a direct pharmacological response to halothane. These observations led to the postulate that halothane by its transient but significant vasoconstrictive action could be a contributing factor to initiate the fulminant reactions occurring in malignant hyperthermia.

Animals↗
PubMed1988

Mechanism of halothane-induced inhibition of isoproterenol-stimulated lipolysis in isolated rat adipocytes.

The effect of halothane on isoproterenol-stimulated lipolysis was determined in isolated rat epididymal fat cells. The maximal lipolytic response (Emax) activated by isoproterenol was 350 +/- 61 nmol of glycerol/10(5) cells/hr with an EC50 of 5.1 X 10(-9) M. When the adipocytes were simultaneously bubbled with 2.5% halothane, the Emax decreased to 158 +/- 43 nmol of glycerol/10(5) cells/hr and the dose response curve for isoproterenol was shifted to the right (EC50 3.5 X 10(-8) M, p less than 0.05). When lipolysis was maximally stimulated with (-)-isoproterenol (10(-6)M), the inhibitory effect of halothane was found to be both dose dependent (IC50 approximately 2.5%, v/v) and reversible following washout. Neither the nonhydrolyzable cAMP analog, 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (2 X 10(-3)M), nor forskolin (10(-6) M) was able to normalize lipolysis in the presence of halothane. The activation of cAMP-dependent protein kinase (EC 2.7.1.37) activity by isoproterenol was not different in halothane-exposed cells when compared to unexposed cells. When control adipocytes were exposed to isoproterenol (10(-6) M), there was a 2.5-fold increase in the activity of hormone-sensitive lipase (EC 3.1.1.3) from 0.64 +/- 0.13 to 1.53 +/- 0.32 pkat (pmol/sec) per mg (p less than 0.005, n = 10). However, in the presence of halothane (2.5%, v/v) isoproterenol stimulation of hormone-sensitive lipase was attenuated by 50% to values of 1.06 +/- 0.23 pkat/mg (p less than 0.01, n = 10). Halothane had no direct inhibitory effect on hormone-sensitive lipase since this enzyme's activity was unaffected when homogenates of isoproterenol-stimulated control cells were incubated with halothane. These studies suggest that halothane impairs the activation of hormone-sensitive lipase by cAMP-dependent protein kinase and in this manner inhibits beta-adrenergic-stimulated lipolysis.

Adipose Tissue↗
PubMedDate not supplied

Effects of cimetidine and ranitidine on halothane metabolism and hepatotoxicity in an animal model.

This study was undertaken to determine the effects of two H2-receptor antagonists, cimetidine and ranitidine, on halothane metabolism and hepatotoxicity in the hypoxic Fisher 344 rat model for halothane hepatitis. In this model, liver injury is caused by toxic intermediates formed during metabolism of halothane by a reductive pathway. Administration of cimetidine (120 mg/kg ip) 20 min prior to anesthesia led to inhibition of the reductive pathway, as assessed by measurement of the exhaled metabolites, 2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, during anesthesia, and urinary fluoride excretion in the 22-hr postanesthesia period. Oxidative metabolism of halothane, assessed by serum bromide concentrations 22 hr postanesthesia, was unaffected. Cimetidine administration provided partial protection against the hepatotoxic effect of halothane, as indicated by serum alanine aminotransferase activities 22 hr postanesthesia. When ranitidine HCl (120 mg/kg ip) was administered prior to anesthesia, reductive metabolism of halothane was unaffected, but the oxidative pathway was slightly inhibited. Ranitidine did not provide protection against halothane-induced liver injury. These results provide additional evidence that halothane hepatotoxicity in the hypoxic rat model is due to toxic intermediates formed during the reductive metabolism of halothane.

Animals↗
PubMed1984

Deuterated halothane--anesthetic potency, anticonvulsant activity, and effect on cerebellar cyclic guanosine 3',5'-monophosphate.

The effect of substituting deuterium for hydrogen in the halothane molecule on anesthetic potency, motor activity, and cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) content was studied in mice. The concentration of halothane required to abolish the righting reflex in 50% of the mice (ED50RR) was chosen as index of anesthetic potency; cerebellar control of motor activity was evaluated by the incidence of isoniazid-induced convulsions. The ED50RR for deuterated (D)-halothane was similar to that of halothane (0.87 +/- 0.04 and 0.88 +/- 0.03 vol%, respectively). Both D-halothane and halothane (0.15-0.90 vol%) protected the mice against isoniazid-induced convulsions and decreased cerebellar cGMP content in a dose-dependent manner. D-halothane and halothane were equipotent on both parameters. Thus deuteration did not alter the anesthetic potency, the anticonvulsant activity, or the effect on cerebellar cGMP content of the anesthetic. Furthermore, the reactivity of the C-H bond is probably not critical for these actions of halothane.

Animals↗
PubMed1983

Hemodynamic responses to nifedipine in dogs anesthetized with halothane.

The interaction of nifedipine and halothane was examined in 19 dogs. Nifedipine (10 micrograms/kg) was infused over 2 min in animals anesthetized with either 1% or 2% halothane. The predominant hemodynamic effect of nifedipine was a short-lived reduction (less than 15 min) in mean blood pressure accompanied by a decrease in systemic vascular resistance. During 2% halothane anesthesia hypotension mean blood pressure was greater (P less than 0.05) 15 and 30 min after nifedipine than during 1% halothane. Nifedipine hypotension was initially (2 min) associated with a 23% increase in heart rate and a 22% increase in cardiac output in animals anesthetized with 1% halothane, but during 2% halothane there was no change in heart rate. Changes in dP/dt and contractile force were minimal after nifedipine in both groups. The clinical implications of this study are that nifedipine given during halothane anesthesia may be associated with significant hypotension and that higher concentrations of halothane attenuate the reflex compensatory increase in heart rate. Doses of halothane and nifedipine must be chosen cautiously when the drugs are used together.

Anesthesia, Inhalation↗
PubMed1984

Inhibitory effect of isoflurane upon oxidative metabolism of halothane.

The effect of isoflurane upon halothane metabolism was studied in rats exposed to mixtures of subanesthetic concentrations of isoflurane (0.015-0.32%) and halothane (0.062%). The extent of halothane metabolism was determined from concentrations of halothane and its metabolites (total nonvolatile fluorine, 1,1,1-trifluoro-2-chloroethane and 1,1-difluoro-2-chloroethylene) in tissues of rats. At the end of exposures lasting 3 hr, distribution of halothane in tissues indicated that the bioavailability of halothane in liver was unaffected by exposure to isoflurane. Isoflurane, however, significantly inhibited the oxidative metabolism of halothane, as indicated by reduced concentrations of total nonvolatile fluorine in tissues. The inhibition is concentration-dependent. Isoflurane enhances the reductive metabolism of halothane, as indicated by increased concentrations of volatile metabolites in liver. Exposure to nitrous oxide (2.2-50%) had no effect on halothane metabolism. The mechanism of the inhibitory effect remains to be explained.

Animals↗
PubMed1983

Uptake and distribution of halothane in infants: in vivo measurements and computer simulations.

We measured uptake of halothane (the fraction of halothane in expired gas divided by the fraction of halothane in inspired gas, FE/FI) with a mass spectrometer over time in 7 infants less than 3 months of age. FE/FI for halothane in these infants increased more rapidly than has been described in adults by others. In addition, we developed a mathematical model for halothane uptake and distribution that incorporates age-dependent anatomic and physiologic parameters (alveolar ventilation, functional residual capacity, cardiac output, brain volume, etc). The model closely predicts FE/FI for halothane measured in the infants. At 5 min observed FE/FI was 0.67, at 15 min observed FE/FI was 0.80, while the predicted FE/FI values were 0.65 and 0.82, respectively. The model predicts that the myocardial and brain halothane concentrations will increase more rapidly in the infant than in the adult. Achievement of high myocardial halothane concentrations early in the anesthetic induction may cause the hypotension and bradycardia commonly seen in infants. Sensitivity of the infant myocardium to halothane would further exacerbate the effect of more rapid myocardial uptake.

Adult↗
PubMed1981

Hepatic blood flow in phenobarbital-pretreated rats during halothane anesthesia and hypoxia.

Centrilobular liver necrosis results when halothane is administered to rats pretreated with phenobarbital. Using radioactive microspheres in Wistar rats weighing 300 to 360 g each, the authors determined cardiac output and hepatic arterial and portal blood flows in normoxic (FlO2 = 0.20) unanesthetized animals pretreated with phenobarbital and in similarly pretreated animals that received halothane with adequate oxygen (FlO2 = 0.50) and while hypoxic (FlO2 = 0.08 to 0.10). Cardiac output averaged 122 +/- 8 ml/min (mean +/- SEM) in unanesthetized normoxic rats and 119 +/- 23 ml/min in unanesthetized hypoxic rats. When halothane, 0.6% in 50% oxygen, was administered cardiac output decreased significantly to 89 +/- 8 ml/min and when halothane was administered during hypoxia cardiac output was decreased further to 80 +/- 11 ml/min. During hypoxia without halothane portal venous blood flow decreased significantly but the percentages of cardiac output delivered to the hepatic artery and portal vein were not significantly different from the normoxic awake animals. When halothane was administered with adequate oxygen the percentage of the cardiac output delivered to the hepatic artery significantly increased but there was no change in absolute blood flow to either the hepatic artery or portal vein. When hypoxic animals received halothane the percentage of the cardiac output delivered to the hepatic artery and portal vein was unchanged but the absolute blood flows to the hepatic artery and portal vein decreased significantly. It is concluded that halothane combined with hypoxia is associated with changes in hepatic blood flow but that these changes are similar to changes caused by hypoxia alone. It is unlikely that hemodynamic factors account for the liver injury seen after halothane and hypoxia in phenobarbital-treated rats.

Anesthesia, Inhalation↗
PubMed1993

Enhancement of gamma-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane.

The volatile general anesthetics halothane and enflurane increased muscimol-stimulated 36Cl- efflux via gamma-aminobutyric acid (GABA)A receptors in rat brain cortical slices and also increased basal 36Cl- efflux in the absence of GABA agonist. The effects occurred in the clinical range of anesthetic concentrations (0.56-1.7 mM halothane and 0.46-1.4 mM enflurane). Both anesthetics induced a slow onset increase in basal 36Cl- efflux rate when added alone with no exogenous GABA agonist. This direct effect of halothane had a biphasic dependence on anesthetic concentrations, with a maximal effect in the range 1.1 to 1.7 mM. Replacing extracellular calcium with magnesium or blocking voltage-gated calcium entry with cobalt (200 microM) altered the direct halothane effect, shifting the concentration-dependence curve to the right. Halothane direct potentiation of chloride flux in the absence of GABA agonist was blocked by the GABAA chloride channel antagonist picrotoxin but not by the GABAA receptor antagonist bicuculline. The halothane potentiation of the muscimol response was detectable at concentrations of 0.56 mM halothane in the assay buffer, and was linear with concentration up to 2.8 mM. The effect was more pronounced at low GABA agonist concentrations, apparently due to an increase in GABA affinity. Lowering the extracellular calcium concentration to micromolar levels did not affect halothane potentiation of muscimol responses. Halothane at similar concentrations increased the high-affinity binding of [3H]muscimol to GABAA receptor sites in rat brain cortical membranes in a calcium-independent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4.

The anesthetic halothane undergoes extensive oxidative and reductive biotransformation, resulting in metabolites that cause hepatotoxicity. Halothane is reduced anaerobically by cytochrome P450 (P450) to the volatile metabolites 2-chloro-1,1-difluoroethene (CDE) and 2-chloro-1,1,1-trifluoroethane (CTE). The purpose of this investigation was to identify the human P450 isoform(s) responsible for reductive halothane metabolism. CDE and CTE formation from halothane metabolism by human liver microsomes was determined by GC/MS analysis. Halothane metabolism to CDE and CTE under reductive conditions was completely inhibited by carbon monoxide, which implicates exclusively P450 in this reaction. Eadie-Hofstee plots of both CDE and CTE formation were nonlinear, suggesting multiple P450 isoform involvement. Microsomal CDE and CTE formation were each inhibited 40-50% by P450 2A6-selective inhibitors (coumarin and 8-methoxypsoralen) and 55-60% by P450 3A4-selective inhibitors (ketoconazole and troleandomycin). P450 1A-, 2B6-, 2C9/10-, and 2D6-selective inhibitors (7,8-benzoflavone, furafylline, orphenadrine, sulfaphenazole, and quinidine) had no significant effect on reductive halothane metabolism. Measurement of product formation catalyzed by a panel of cDNA-expressed P450 isoforms revealed that maximal rates of CDE formation occurred with P450 2A6, followed by P450 3A4. P450 3A4 was the most effective catalyst of CTE formation. Among a panel of 11 different human livers, there were significant linear correlations between the rate of CDE formation and both 2A6 activity (r = 0.64, p < 0.04) and 3A4 activity (r = 0.64, p < 0.03). Similarly, there were significant linear correlations between CTE formation and both 2A6 activity (r = 0.55, p < 0.08) and 3A4 activity (r = 0.77, p < 0.005). The P450 2E1 inhibitors 4-methylpyrazole and diethyldithiocarbamate inhibited CDE and CTE formation by 20-45% and 40-50%, respectively; however, cDNA-expressed P450 2E1 did not catalyze significant amounts of CDE or CTE production, and microsomal metabolite formation was not correlated with P450 2E1 activity. This investigation demonstrated that human liver microsomal reductive halothane metabolism is catalyzed predominantly by P450 2A6 and 3A4. This isoform selectivity for anaerobic halothane metabolism contrasts with that for oxidative human halothane metabolism, which is catalyzed predominantly by P450 2E1.

Anesthetics, Inhalation↗
PubMed1997

The effect of chronic nicotine and its withdrawal on ED50 inspired halothane requirement in rats.

BACKGROUND: Based on previously observed antinociceptive effect of chronic nicotine treatment in rats, the authors measured the ED50 inspired halothane, concentrations in rats having withdrawn from chronically infused nicotine, and in control rats. METHODS: Rats in nicotine group (n = 19) were chronically exposed to nicotine (6 mg/kg/day for 28 days) infusion via Alzet osmotic pumps. Those in the control group (n = 16) were subjected to a sham operation. In each group, half of the rats was used one month later to explore the effect of nicotine withdrawal. Halothane in oxygen was delivered at a rate of 2 L/min to a box measured 2,912 cm3. The ED50 halothane concentration, measured by mass spectrophotometry, was a midway gas tension at which 50% of rats responded to the tail pinching applied to the distal third of the tail for 30 s. RESULTS: In nicotine group, the results showed a lower concentration of ED50 inspired halothane on days 1 and 3 in the first week (p < 0.05). In the control group, repeated exposures to halothane gradually decreased the ED50, reaching lowest value on day 7 (p < 0.05 compared to day 1). Nicotine withdrawal did not alter the ED50 concentration of halothane in test rats compared with control rats. CONCLUSIONS: We conclude that chronic nicotine infusion could temporarily decrease the ED50 concentration of inspired halothane, and withdrawal of nicotine did not modify the ED50 concentration of halothane. In addition, the ED50 halothane concentration might be influenced by stress.

Anesthetics, Inhalation↗
PubMed2000

Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo.

PURPOSE: In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. METHODS: Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. RESULTS: General anesthesia with halothane alone decreased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. CONCLUSION: These results suggest that halothane potently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.

Journal Article↗
PubMed1996

Impaired bile flow and disordered hepatic calcium homeostasis are early features of halothane-induced liver injury in guinea pigs.

To characterize the early events in liver injury produced by halothane, experiments were performed in genetically susceptible guinea pigs 19 hours after halothane exposure. Serum bile acid concentrations were fourfold increased in halothane-exposed animals compared with controls. In isolated perfused liver experiments, livers from halothane-exposed animals did not differ in hepatic oxygen uptake or in perfusion pressure at the end of experiments, but bile flow and biliary bile salt concentrations were reduced. Hepatic calcium content was increased in halothane-exposed guinea pigs compared with controls, and further experiments were performed to explore the reason for this. As determined by infusion of 45Ca to steady-state perfusate concentrations, hepatic calcium clearance was increased in halothane-exposed guinea pigs compared with controls (0.37 +/- 0.06 vs. 0.28 +/- 0.02 mL/min, P < .01). Decreased biliary excretion of calcium was also noted and was entirely attributable to reduced bile flow. However, although decreased excretion contributed to hepatic accumulation of calcium, it was quantitatively less important than enhanced hepatic uptake. As indicated by passage of a bolus of horseradish peroxidase from perfusate into bile, hepatic tight junction permeability was increased five-fold after halothane exposure. It is concluded that cholestasis, as exemplified by reduced bile flow, is an early feature of the liver injury produced by halothane in guinea pigs and is associated with increased tight junction permeability. Although the decrease in bile flow contributes to an early increase in hepatic calcium content, entry of calcium from the perfusion compartment is quantitatively more important.

Animals↗
PubMed1990

Effect of chronic halothane exposure on lipid peroxidation, osmotic fragility and morphology of rat erythrocytes.

Effect of chronic halothane exposure on hepatic and erythrocyte lipid peroxidation and erythrocyte osmotic fragility and morphology were determined in rats exposed to 0.4% halothane, 8 h per day for 40 days. Hepatic lipid peroxidation was increased in the halothane-treated group compared to controls. Lipid peroxidation was not increased by halothane exposure in erythrocytes without hydrogen peroxide, but after peroxide supplementation lipid peroxidation increased more in the erythrocytes of halothane-exposed rats than in control rats. We have observed significant morphological changes in erythrocytes from halothane-treated rats. In addition, erythrocytes of halothane-treated rats were more fragile in saline solutions compared to those of controls. Our results suggest that chronic halothane exposure is not only hepatotoxic but also affects erythrocyte membrane structure and stability.

Administration, Inhalation↗
PubMed1990

Embryotoxic/teratogenic potential of halothane.

The embryotoxic/teratogenic potential of halothane was evaluated on the basis of available data obtained in an extensive literature search. It was found that halothane induced ultrastructural visible changes in the offspring of rats exposed to concentrations of 10 ppm during gestation. These consisted of degenerative changes in the cerebral cortex and, in particular, the weakening of cell membranes and the vacuolisation of the Golgi-complex. Macroscopically visible morphological changes were seen in rats only after exposure to concentrations equivalent to 320-fold (1600 ppm) the MAK value (maximum concentration value at the workplace). Furthermore, behavioural disorders were seen when exposure to concentrations greater than or equal to 10 ppm occurred during gestation and after parturition. In mice, only macroscopical investigations were performed. The first disturbances scored were only visible as retardation in the offspring, and occurred after exposure to concentrations of halothane 200-fold (1000 ppm) the MAK-value. In the rabbit, anaesthetic concentrations of 22000 ppm halothane did not result in an embryotoxic/teratogenic effect. The individual epidemiological findings in humans were discussed controversially. The studies are inconclusive in establishing an embryotoxic/teratogenic risk following sole exposure to halothane at the MAK level, since mixed exposures occurred and data on the concentrations of halothane in the inhaled air were missing. Therefore, the decision on whether halothane can impair intrauterine development is primarily based on the animal experimental findings. As long as a threshold value has not been established for the observed lesions, halothane should not be inhaled during pregnancy.

Abnormalities, Drug-Induced↗
PubMed1999

Anesthetic modulation of myocardial ischemia and reperfusion injury in pigs: comparison between halothane and sevoflurane.

PURPOSE: Halothane offers protection against the reperfusion injury of the myocardium. This study compared sevoflurane with halothane in its potential to modulate the effects of acute severe ischemia and reperfusion on the myocardium. METHODS: Experiments were conducted on 25 pigs. Anesthesia consisted of thiopental, vecuronium and fentanyl. The lungs were mechanically ventilated with oxygen and nitrogen. Animals were randomly allocated to receive either I MAC halothane or sevoflurane. A control group received fentanyl and pentobarbital. Regional myocardial function was measured with sonomicrometers. The left anterior descending coronary artery was occluded for 15 min followed by 60 min reperfusion. RESULTS: Neither halothane nor sevoflurane protected the heart against the effects of acute and severe regional myocardial ischemia. During reperfusion, 89% of the animals receiving sevoflurane suffered from ventricular fibrillation compared with 30% in the halothane group (P < 0.005). Five minutes into the reperfusion period the animals subjected to halothane anesthesia demonstrated an 88% recovery in regional myocardial systolic function while in the sevoflurane group the recovery was 40% of pre-ischemic control (P < 0.05). CONCLUSION: Halothane is associated with less reperfusion arrhythmias and, in addition, recovery of regional myocardial function during reperfusion was more rapid in the presence of halothane than with sevoflurane.

Adjuvants, Anesthesia↗
PubMed1998

Ca2+ channel modulation alters halothane-induced depression of ventricular myocytes.

PURPOSE: This study examined the direct myocardial depressant effect of halothane and determined whether an L-type Ca2+ channel agonist and antagonists altered the myocardial depression induced by halothane in cultured rat ventricular myocytes. METHODS: Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6 to 7 days. The myocytes were stabilized in a serum-free medium, and the spontaneous beating rate and amplitude were measured. To assess the halothane-induced conformational changes in L-type Ca2+ channel, receptor binding study was performed using a dihydropyridine derivative, [3H] PN 200-110, in cardiac membrane preparation. RESULTS: Halothane (1%, 2%, 3%, 4%) decreased the beating rate and amplitude in a concentration-dependent manner (P < 0.05). The myocardial depressant effects of halothane were potentiated by nifedipine or verapamil (P < 0.05). Bay K 8644, an L-type Ca2+ channel agonist, completely prevented the halothane-induced depression in amplitude (P < 0.05), but affected the beating rate less. Adding halothane (2%) decreased (P < 0.05) the maximum binding site density for [3H] PN 200-110 (from 198.6 +/- 23.7 fmol.mg-1 protein to 115.3 +/- 21.6 fmol.mg-1 protein) but did not affect binding affinity (from 0.461 +/- 0.077 nM to 0.307 +/- 0.055 nM). CONCLUSION: The reduction of Ca2+ current via sarcolemmal L-type Ca2+ channel, probably due to conformational changes in dihydropyridine binding sites, plays an important role in halothane-induced myocardial depression in living heart cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2005

Multiple actions of halothane on contractile response to noradrenaline in isolated mesenteric resistance arteries.

Halothane, a volatile anaesthetic, produces systemic hypotension and significantly alters organ blood flow. Isometric force was recorded in isolated rat small mesenteric arteries to investigate its action on contractile response to noradrenaline, the sympathetic neurotransmitter. Halothane (1-5%) enhanced contractile response to noradrenaline in the endothelium-intact arteries, but had little influence in the endothelium-denuded arteries. However, halothane consistently inhibited the noradrenaline response in the endothelium-denuded arteries pretreated with ryanodine (10 microM). The enhancement of the contractile response to noradrenaline in the endothelium-intact arteries was unaffected by treatment with N(G)-nitro L-arginine, tetraethylammonium, apamin, charybdotoxin, indomethacin, diclofenac, nordihydroguaiaretic acid, BQ-123, BQ-788, losartan, ketanserin, or superoxide dismutase. Halothane prolonged vasorelaxation after washout of noradrenaline in the endothelium-denuded arteries. Both ryanodine and vanadate (0.1-0.3 mM), a putative inhibitor of the plasma membrane Ca2+-ATPase, also prolonged the vasorelaxation. Halothane still prolonged the vasorelaxation in the ryanodine-treated arteries, but not in the vanadate-treated arteries. Halothane decreased the pD2 value for the pCa-force relation in the beta-escin-permeabilised, endothelium-denuded arteries. Halothane appears to influence contractile response to noradrenaline through multiple actions including endothelium-dependent enhancing, endothelium-independent enhancing, and endothelium-independent inhibitory actions. Nitric oxide, endothelium-derived hyperpolarising factor, cyclooxygenase products, lipoxygenase products, endothelin-1, angiotensin-II, serotonin, and superoxide anions are not involved in the endothelium-dependent enhancement. The endothelium-independent enhancement is presumably due to its ability to stimulate Ca2+ release from the ryanodine-sensitive intracellular stores, while the endothelium-independent inhibition is due, at least in part, to depressed Ca2+-activation of contractile proteins. Halothane may inhibit the plasma membrane Ca2+-ATPase of vascular smooth muscle cells.

Anesthetics, Inhalation↗