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1.
Tetsumi Sato Kazuyoshi Hirota Akitomo Matsuki Elemer K. Zsigmond Sara F. Rabito 《Journal canadien d'anesthésie》1996,43(2):172-178
Purpose
Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca++-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of α-adrenoceptors to the relaxant effect of D in vitro.Methods
Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode’s solution, aerated with a mixture of 95% O2 and 5% CO2 at 37°C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph.Results
We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 × 10?6 M D blocked the effect of 10?4 M 5-HT by 44.1 ± 4.3% and at 2.5 × 10?6 M by 63.8 ± 3.8%. Similarly, at 5.0 × 10?6 M concentration, D blocked the effect of 10?5 M H by 27.7 ± 5.3% and at 10?5 M by 56.2 ± 2.6%. Furthermore, 5 ×10?6 M of D reduced the contractions produced by 10?7 M C by 37.1 ± 3.0% and 70?5 M of D by 76.1 ± 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (70?6 M) affected neither 5-HT-induced contractions nor the inhibition by D.Conclusion
Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways. 相似文献2.
3.
Zsigmond EK 《Anesthesia and analgesia》2004,98(5):1504; author reply 1504-1504; author reply 1505
4.
Esmolol, a new cardioselective beta adrenergic blocker inhibits plasmacholinesterase activity in vitro. The concentration of esmolol hydrochloride that inhibits by 50 per cent the hydrolysis of 50.0 µnol·L?1 benzoylcholine hydrochloride by 1:200 diluted, heparinized pooled plasma of six healthy volunteers at 37° C and 240 nm, determined by the ultraviolet spectrophotometric method of Kalow, was 50 µmol·?1. Esmolol’s primary metabolite, 3-(4-(2-hydroxy-3-(isopropylamino)propoxy)-phenyllpropionic acid, had an l5 = 190 µnol·L?1 . The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 µg·kg?1. min?1 for 4 minutes were 58.6 ± 6.2 µmol·hr?1·ml?1 (mean ± SE) before and 55.1 ± 6.6 µmol·hr?1·ml?1 after the infusion. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 µg·kg?1·min?1 for two minutes and 200 µg·kg?1·min?1 for an additional two minutes were 70.2 ± 8.9µmol·hr?1·ml?1 before and 69.1 ± 9.5 µmol·hr?1. ml?1 after the infusion. The pre- and post-infusion plasmacholinesterase activities were not significantly different. Since plasmacholinesterase is responsible for the hydrolysis of succinylcholine and that of the ester-type local anaesthetics this lack of in vivo interaction of esmolol with the hydrolysis of these drugs should be further confirmed by experiments with these combinations in man. 相似文献
5.
6.
Istvan Hüttner Marie-Claude Badonnel Gabriella Elemer Guilio Gabbiani 《Experimental and molecular pathology》1979,31(1):191-200
Intimal changes of rat thoracic aorta were reviewed in early and late phases of two selected models of hypertension: (1) aortic ligation, a model associated with high plasma renin level in the early phase, but normal or low plasma renin levels in the late phase of hypertension; (2) high salt diet and unilateral nephrectomy, a model known to result in slowly rising blood pressure associated with continuously low levels of plasma renin. In hypertension produced by aortic ligation, the aortic endothelium showed an increased permeability to horseradish peroxidase in the early phase which was not observed in the late phase. Endothelial cells were markedly hypertrophic and contained a cytoplasmic contractile apparatus in the early phase, while they were smaller and showed less prominent microfilaments in the late phase of hypertension. In the late phase, accumulation of connective tissue matrix was noted, in addition in the subendothelial layer. In hypertension induced by high salt diet and unilateral nephrectomy, there was some endothelial cell hypertrophy at the early phase, but changes in permeability and in cytoplasmic contractile filaments were not detected at any phase. The most prominent morphological finding in this model was a progressive accumulation of connective tissue matix in the subendothelial layer. These data indicate that the aortic endothelium may react differently to varying hypertensive stimuli and may adapt to high levels of blood pressure. 相似文献
7.
Morphologic and functional changes of the aortic intima during experimental hypertension. 总被引:9,自引:6,他引:3
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G. Gabbiani G. Elemer C. Guelpa M. B. Vallotton M. C. Badonnel I. Hüttner 《The American journal of pathology》1979,96(2):399-422
The morphology and permeability to horseradish peroxidase of the rat aortic intima have been investigated in three experimental models of hypertension having different values of plasma renin content and plasma aldosterone level. During hypertension the aortic endothelium shows three main changes: 1) increased arithmetic mean thickness, with prominent rough endoplasmic reticulum and polyribosomes; 2) the appearance of actin microfilament bundles; and 3) increased permeability to horseradish peroxidase. These changes are not present in all models, do not appear to depend on hypertension per se, and are independent of each other. The subendothelial layer of hypertensive animals shows an increased thickness that appears to be correlated with an increase of endothelial cell volume. Our results suggest that: 1) the aortic intima reacts differently to different types of hypertension, and 2) factors other than hypertension per se play a role in the development of vascular changes observed in animals with elevated blood pressure. 相似文献
8.
Szabadi E 《British journal of clinical pharmacology》2006,61(6):761-766
The past decade has witnessed an explosion of knowledge about the neural mechanisms that control sleep and arousal, triggered by two discoveries relating to the sleep disorder narcolepsy. Narcolepsy is caused by the loss of orexin-containing neurons in the hypothalamus, and a novel nonstimulant wakefulness-promoting drug, modafinil, alleviates excessive day-time sleepiness associated with the disorder. The level of arousal is controlled by an intricate interplay between distinct wakefulness- and sleep-promoting nuclei situated in the hypothalamus and brainstem and the interconnections between the nuclei and the neurotransmitters involved have been mapped. Wakefulness-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei and possibly the dopaminergic ventral tegmental area. The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. Currently available and future drugs exert their therapeutic effects in the three major classes of sleep disorder (insomnia, hypersomnia, parasomnia) by modifying neurotransmission at distinct sites within the arousal-controlling neuronal network. This enables classification of therapeutic drugs for sleep disorders on the basis of their modes of action: drugs that interact with the GABAergic sleep-promoting system, drugs that interact with different wakefulness-promoting systems and drugs that modulate the level of arousal by mechanisms that do not initially involve the basic network (e.g. melatonin, adenosine). The development of novel therapeutic drugs for sleep disorders is based on the synthesis of molecular/cellular mechanisms and the sites of action within the arousal-controlling neuronal network. 相似文献
9.
The permeability to Horseradish Peroxidase (HRP) of the rat caudal artery at the level of spontaneous lesions was evaluated by electron microscopy and compared with that of lesions experimentally induced by pinching or internal scraping of the caudal and iliac arteries. No HRP reaction product is observed in the extracellular space of the arterial wall when (i) the internal elastic lamina (IEL) and the endothelium are absent, (ii) the IEL is maintained and the endothelium is absent and (iii) the IEL is absent and the endothelium has regenerated. That HRP does enter the arterial wall in cases of gross endothelial damage is shown by its selective retention in damaged smooth muscle cells in such cases. In contrast, HRP reaction product is detected in the subendothelial space when the IEL is maintained and is covered by a regenerating or recently regenerated endothelium. Furthermore, the amount of tracer visualized under the same experimental conditions is greater in the iliac than in the caudal artery. We conclude that the detection of HRP in the subendothelial space of the artery wall requires the presence of regenerating or recently regenerated endothelial cells lying on an intact IEL. It is thus not simply related to endothelial permeability but depends also upon the retention of HRP by extracellular substances. In addition, the quantity of marker retained varies between different sites in the arterial tree. 相似文献
10.
Ebony R Samuels Ruihua H Hou Robert W Langley Elemer Szabadi Christopher M Bradshaw 《Neuropsychopharmacology》2007,32(11):2405-2421
A sudden loud sound evokes an electromyographic (EMG) response from the orbicularis oculi muscle in humans together with an auditory evoked potential (AEP) and an increase in skin conductance (SC). Startle responses are inhibited by weak prepulses (prepulse inhibition, (PPI)) and may also be modified by the level of alertness. We compared the sedative drug clonidine and the alerting drug modafinil on sound-evoked EMG, AEP, and SC responses, on the PPI of these responses and on level of arousal and autonomic functions. Sixteen healthy male volunteers participated in four weekly sessions (clonidine 0.2 mg, modafinil 400 mg, their combination, placebo) in a double-blind, cross-over, balanced design. Responses were evoked by sound pulses of 115 and 85 dB (PPI) for 40 ms and recorded conventionally. Level of alertness, autonomic functions (pupil diameter, blood pressure, heart rate, salivation, temperature) and the plasma levels of the hormones prolactin, thyroid-stimulating hormone and growth hormone were also measured. Data were analyzed with analysis of variance with multiple comparisons. Both prepulses and clonidine attenuated all three startle responses and modafinil antagonized clonidine's effects on the EMG and AEP responses. None of the drugs affected PPI. Clonidine showed sedative and sympatholytic effects, and modafinil showed alerting and sympathomimetic effects. In conclusion, startle responses were susceptible not only to PPI but also to the level of arousal. 相似文献