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Chronopharmacology and its impact on antihypertensive treatment. 时间药理学及其对降压治疗的影响。
B Lemmer

Circadian rhythms have been documented throughout the plant and animal kingdom at every level of eukariotic organization. Circadian rhythms are endogenous in nature, driven by oscillators or clocks, and persist under free-running (e.g. constant darkness) conditions. The genes expressing the biological clock have been identified in various species. The important feature of endogeneous biological rhythms is their anticipatory character. Rhythmicity inherent to all living systems, allows them to adapt more easily and to better survive under changing environmental conditions during the 24 hours of a day as well as during changing seasons. Having this in mind it is easy to conceive that not only must the right amount of the right substance be at the right place, but also this must occur at the right time. Also in man nearly all functions of the body including those influencing pharmacokinetic parameters such as drug absorption and distribution, drug metabolism and renal elimination display significant daily variations. Also the onset and symptoms of diseases such as coronary infarction, angina pectoris, stroke, ventricular tachycardia are circadian phase dependent. Myocardial infarction and angina attacks as well as silent ischemias (ST-segment depression) in stable angina pectoris have an early morning peak between 8-12 h. In contrast, ECG abnormalities and angina attacks in variant angina mainly occur at night. Blood pressure and heart rate in normotensives and essential (primary) hypertensive patients display highest values during daytime followed by a nightly drop and an early morning rise. In about 70% of forms of secondary hypertension (e.g. renal disease, hyperthyroidisms, hormonal diseases, gestational hypertension), however, this rhythmic pattern is abolished or even reversed exhibiting nightly peaks in blood pressure. This form of hypertension is accompanied by increased end organ damages. Thus, different subtypes of a disease (angina pectoris, hypertension) can display different circadian patterns in symptoms. These observations are a challenge for basic and clinical research to get a better understanding on the underlying mechanisms of regulation. Moreover, they call for a circadian time-specified drug treatment. From above it is evident that pharmacokinetics may also not be constant within a day. Chronopharmacokinetics have been shown for several cardiovascular active drugs (propranolol, nifedipine, verapamil, enalapril, isosorbide-5-mononitrate, digoxin, etc.). Far more drugs were shown to display significant daily variations in their effects (chronopharmacodynamics, chronotoxicology) even after chronic application or constant infusion. In conclusion, there is clear evidence that the dose/concentration-response relationship of drugs can be significantly dependent on the time of day. Thus, circadian time has to be taken into account as an important variable influencing a drug's pharmacokinetics and/or its effects or side effects.

在整个植物和动物王国中,在真核生物组织的每一个层次上都有昼夜节律的记录。昼夜节律本质上是内源性的,由振荡器或时钟驱动,并在自由运行(例如持续黑暗)的条件下持续存在。表达生物钟的基因已经在许多物种中被鉴定出来。内源性生物节律的重要特征是其预见性。所有生命系统固有的节律性使它们能够更容易地适应和更好地在一天24小时不断变化的环境条件下以及在变化的季节中生存。考虑到这一点,我们就很容易想到,不仅要在适当的地方放置适当数量的适当物质,而且要在适当的时间出现。此外,人体几乎所有功能,包括那些影响药代动力学参数的功能,如药物吸收和分布、药物代谢和肾脏消除,每天都有显著变化。此外,诸如冠状动脉梗塞、心绞痛、中风、室性心动过速等疾病的发病和症状也与昼夜节律相依赖。稳定型心绞痛的心肌梗死和心绞痛发作以及无症状性缺血(st段下降)在清晨8-12小时之间出现高峰,而变异性心绞痛的心电图异常和心绞痛发作主要发生在夜间。正常血压和原发性高血压患者的血压和心率在白天最高,随后夜间下降,清晨上升。然而,在大约70%的继发性高血压(如肾病、甲状腺功能亢进、激素疾病、妊娠期高血压)中,这种节律模式被取消或甚至逆转,表现为夜间血压峰值。这种形式的高血压伴随着终末器官损伤的增加。因此,一种疾病的不同亚型(心绞痛、高血压)在症状上可以表现出不同的昼夜节律模式。这些观察结果对基础和临床研究提出了挑战,以更好地了解调节的潜在机制。此外,他们还呼吁采用昼夜节律时间指定的药物治疗。由此可见,药代动力学在一天内也可能不是恒定的。一些心血管活性药物(心得安、硝苯地平、维拉帕米、依那普利、异山梨酯-5-单硝酸盐、地高辛等)的时间药代动力学已被证实。更多的药物显示出显著的每日变化的效果(时间药效学,时间毒理学),甚至在长期应用或持续输注后。总之,有明确的证据表明,药物的剂量/浓度-反应关系可以显著依赖于一天中的时间。因此,必须将昼夜节律时间作为影响药物药代动力学和/或其作用或副作用的重要变量加以考虑。
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引用次数: 0
Renal excretory function in conscious Long Evans and vasopressin deficient (Brattleboro) rats after endothelin-A receptor inhibition. 内皮素a受体抑制后,Long Evans和血管加压素缺乏(Brattleboro)大鼠的肾脏排泄功能
R Girchev, P Markova, D Mikhov, N Natcheff

All experiments were performed on conscious, freely moving male Long Evans as well as Diabetes incipidus (Brattleboro) rats (300-320 g). The endothelin-A (ETA) receptor antagonist BQ-123 (Neosystem) was administered through femoral vein cannula. Arterial blood pressure was measured trough femoral artery catheter. The bladder was cannulated for urine collection via a small suprapubic incision. After a 40 min control period BQ-123 infusion (16.4 nmol/kg/min, 25 microliters/min) was started and continued for 50 min. The effect of 32.8 nmol/kg/min BQ-123 infused in conscious Brattleboro rats was also investigated. Plasma and urine concentrations of sodium, potassium and chloride as well as osmolality were determined. Glomerular filtration rate (GFR) was estimated using the clearance of endogenous creatinine. Endothelin-A receptor inhibition by 16.4 nmol/kg/min BQ-123 infusion in conscious Long-Evans rats decreased urine flow rate by 38.4% (p < 0.02) and increased urine osmolality by 30.3% (p < 0.05). Sodium, potassium, chloride excretion did not alter. Endothelin-A receptor inhibition by 16.4 nmol/kg/min and by 32.8 nmol/kg/min BQ-123 infusion in conscious Brattleboro rats did not produce any change in urine flow rate, urine osmolality or excretion of the electrolytes studied. Endothelins acting via ETA receptors may function as an inhibitor of water reabsorption in the kidneys of conscious rats.

所有实验均在有意识、可自由活动的雄性Long Evans和糖尿病(Brattleboro)大鼠(300-320 g)身上进行。内皮素- a (ETA)受体拮抗剂BQ-123 (Neosystem)通过股静脉插管给药。通过股动脉导管测量动脉血压。膀胱经耻骨上小切口插管收集尿液。对照组开始注射BQ-123 (16.4 nmol/kg/min, 25微升/min),持续注射50 min,观察32.8 nmol/kg/min BQ-123对清醒Brattleboro大鼠的影响。测定血浆和尿液中钠、钾、氯的浓度以及渗透压。肾小球滤过率(GFR)通过内源性肌酐清除率来估计。16.4 nmol/kg/min BQ-123对清醒大鼠内皮素a受体的抑制作用使其尿流率降低38.4% (p < 0.02),尿渗透压升高30.3% (p < 0.05)。钠、钾、氯的排泄没有改变。16.4 nmol/kg/min和32.8 nmol/kg/min输注BQ-123对有意识的Brattleboro大鼠的内皮素- a受体的抑制作用没有引起尿流率、尿渗透压或电解质排泄的任何变化。内皮素通过ETA受体的作用可能作为清醒大鼠肾脏水重吸收的抑制剂。
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引用次数: 0
Spectral analysis of heart rate and arterial pressure variability after nitric oxide synthase inhibition. 一氧化氮合酶抑制后心率和动脉压变异性的频谱分析。
D Mikhov, P Markova, R Girchev

The experiments were performed on male, conscious Wistar rats. Femoral arterial pressure was registered by Statham GOULD P23 ID pressure transducer connected to MP 100WS BIOPAC work station after analog to digital conversion during 40 minutes long control period. Nitric oxide synthase inhibition was performed by injection of 100 microliters, 10 mg/kg b.w. N-omega-nitro-L-arginine methyl ester (L-NAME) in saline through femoral vein catheter. Twenty minutes later arterial pressure registration was started and was continued for 40 minutes. The pulse-by-pulse values of systolic, diastolic and mean arterial pressure as well as the pulse intervals were measured by peak and rate detectors of the AcqKnowledge 2.0 software. Row data were processed using a virtual instrument developed in our laboratory in the graphical programming environment Lab VIEW 3.1.1. L-NAME increased systolic, diastolic and mean arterial pressure by 16.6%, 25% and 35%, respectively. The PMF/PHF ratio in heart rate spectrum decreased, indicating an increased vagal effect on the heart. Nitric oxide synthase inhibition increased the low-frequency component of systolic arterial blood pressure variability by 39.5%. Nitric oxide is a physiological regulator of rapid fluctuations of arterial blood pressure.

实验是在有意识的雄性Wistar大鼠身上进行的。在40分钟的控制期内,通过连接到mp100ws BIOPAC工作站的Statham GOULD P23 ID压力传感器进行模拟-数字转换,记录股动脉压力。通过股静脉导管在生理盐水中注射n -omega-硝基- l -精氨酸甲酯(L-NAME) 100微升,10 mg/kg b.w抑制一氧化氮合酶。20分钟后开始动脉压记录并持续40分钟。采用AcqKnowledge 2.0软件的峰值检测器和速率检测器,测量收缩压、舒张压和平均动脉压的逐脉值以及脉间期。使用我们实验室在图形化编程环境Lab VIEW 3.1.1中开发的虚拟仪器对行数据进行处理。L-NAME使收缩压、舒张压和平均动脉压分别升高16.6%、25%和35%。心率谱PMF/PHF比值降低,表明迷走神经对心脏的影响增强。一氧化氮合酶抑制使收缩压变异性的低频成分增加了39.5%。一氧化氮是动脉血压快速波动的生理调节剂。
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引用次数: 0
Non-invasive registration of the aboral and oral spreading of the gastroduodenal peristaltic activity (experimental and clinical investigations). 无创地记录胃十二指肠的肠蠕动活动(实验和临床研究)。
E Atanassova, B Damianov, P Gurkov, V Kolev

The electrical activity of the stomach and the upper part of the small intestine of healthy volunteers and patients with nausea and vomiting was recorded non-invasively on an original electrogastrograph. Two kinds of waves were distinguished according to their amplitude: low-amplitude waves, corresponding to the period of quiescence of migrating myoelectrical complex (MMC) and about twice higher in amplitude waves, characterising the periods of activity of MMC (peristaltic activity). There was also some difference between the low- and high-amplitude waves from the small intestine. Sequence of high-amplitude waves recorded from the stomach was followed usually by sequence of high-amplitude waves from the small intestine, presenting the aboral spreading of an activity period of MMC from the stomach to the small intestine. In some patients however, high-amplitude waves were led off first from the duodenal record and after that high-amplitude waves appeared in the gastric record. This suggests an oral spreading of the peristaltic activity (antiperistalsis). Experimental model of antiperistalsis was performed on dogs with chronically implanted electrodes on the gastric and duodenal muscle wall. Carbachol 5 micrograms/kg i.m. evoked bursts of spike potentials first with duodenal slow waves and after that with the gastric slow potentials. The antiperistaltic spreading of the spike activity in dog corresponded to the appearance of high-amplitude waves first in the record of the human small intestine, followed by sequence of high-amplitude waves in the stomach. Thus, the non-invasive recording of the electrical activity of the stomach and small intestines gives reliable information about the direction of the spreading of the peristaltic activity.

健康志愿者和恶心呕吐患者的胃和小肠上部的电活动在原始胃电图上无创记录。根据其振幅区分出两种波:低振幅波,对应于迁移肌电复合体(MMC)的静止期;振幅高约两倍的波,表征MMC(蠕动活动)的活动期。来自小肠的低振幅波和高振幅波之间也存在一些差异。从胃记录的高振幅波序列之后通常是从小肠记录的高振幅波序列,显示MMC从胃到小肠的一个活跃期的体外扩散。然而,在一些患者中,高振幅波首先从十二指肠记录中被引出,然后在胃记录中出现高振幅波。这表明口腔蠕动活动(反蠕动)扩散。采用胃、十二指肠肌壁长期植入电极,建立大鼠抗蠕动实验模型。5 μ g /kg灌胃氨基戊二醇可诱发先十二指肠慢波后胃慢波的脉冲电位。狗的脉冲活动的反蠕动扩散与人类小肠记录中首先出现的高振幅波相对应,其次是胃中的一系列高振幅波。因此,对胃和小肠电活动的非侵入性记录提供了关于蠕动活动扩散方向的可靠信息。
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引用次数: 0
Frog muscle fibre action potential and different extracellular calcium concentration at lowered pH in the medium. 低pH条件下蛙肌纤维动作电位与细胞外钙浓度的关系。
N Radicheva, K Mileva, V Martinov

This article is mainly concerned with the influence of Ca2+[o in acidified extracellular medium on the intracellular action potentials (ICAPs) and total ionic current (Ii) during ICAP of isolated skeletal muscle fibre. The bundles of frog muscle fibres were bathed in Ringer's solution with standard Ca2+[o at pH 6.5 after which the fibres were exposed for 30 min to Ca(2+)-free solution and Ca(2+)-enriched solution at pH 6.5. The ICAPs in standard Ca2+[o solution (control) and after exposure for 30 min to Ringer's solutions with different Ca2+[o at pH 6.5 were recorded and the Ii during ICAP was calculated. The ICAP amplitude from the fibres in Ca(2+)-free solutions at pH 6.5 showed a significant increase vs. control, while the time characteristics if the ICAPs in different Ca2+[o decreased except for the ICAP depolarization phase duration in Ca(2+)-enriched solution. The Ii alterations reflect ICAP changes. It was suggested that the changed Ca2+[o at pH 6.5 compensated to some extent the observed inhibitory effect of lowered pH on ICAP parameters in solution with standard Ca2+[o.

本文主要研究了酸化细胞外介质中Ca2+[o对离体骨骼肌纤维细胞内动作电位(ICAPs)和总离子电流(Ii)的影响。将青蛙肌肉纤维束浸泡在pH为6.5的标准Ca2+[o]林格氏溶液中,然后将纤维暴露在pH为6.5的无Ca(2+)溶液和富Ca(2+)溶液中30分钟。记录标准Ca2+[o溶液(对照)和pH 6.5条件下不同Ca2+[o的林格溶液暴露30min后的ICAP,并计算ICAP过程中的Ii。在pH为6.5的无Ca(2+)溶液中,纤维的ICAP振幅与对照相比有显著增加,而在不同Ca2+[o)溶液中,ICAP的时间特征除Ca(2+)富集溶液中的ICAP去极化相持续时间外,均有所减少。Ii的变化反映了ICAP的变化。结果表明,pH值为6.5时Ca2+[o的变化在一定程度上补偿了pH值降低对标准Ca2+[o溶液中ICAP参数的抑制作用。
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引用次数: 0
alpha-Tocopherol and reduced glutathione deficiency and decreased deformability of erythrocytes after thermal skin injury. -生育酚和谷胱甘肽缺乏症,以及皮肤热损伤后红细胞变形能力降低。
G Bekyarova, T Yankova

Burns are followed by oxidative changes in red blood cells, probably as a result of ischemia/reperfusion which takes place in the microvasculature of the injured tissues. This leads to a marked decrease in the erythrocyte deformability, one of the most prominent factors for haemorheological disorders in the early post-burn period. We found that at the 24 th hour after burn skin injury of rats, the decrease in erythrocyte deformability was accompanied by an increase of fluorescent product levels in red blood cells. The erythrocyte systems for antioxidative protection fail to control the oxidative burst after burning. This was due to the decreased concentration of vitamin E (a-tocopherol) and reduced glutathione (GSH) and the increased oxidized glutathione (GSSG) in red blood cells. Both alpha-tocopherol and GSH-deficiency potentiate the susceptibility of red blood cells to oxidative membrane injury, and decrease the deformability of thermally affected erythrocytes. Treatment with alpha-tocopherol (20 ml/kg b.m., immediately after thermal skin injury) prevented the vitamin E reduction and peroxidative membrane damage of erythrocytes and improved their deformability. These results provided strong evidence that the decreased erythrocyte deformability is partly related with alpha-tocopherol deficiency and oxidative membrane damage of red blood cells in the early post burn period.

烧伤后红细胞发生氧化变化,这可能是损伤组织微血管发生缺血/再灌注的结果。这导致红细胞变形能力显著降低,这是烧伤后早期血液流变学障碍的最重要因素之一。我们发现,大鼠皮肤烧伤后24小时,红细胞变形能力下降,同时红细胞荧光产物水平升高。红细胞系统的抗氧化保护不能控制燃烧后的氧化爆发。这是由于红细胞中维生素E (a-生育酚)和谷胱甘肽(GSH)的浓度降低以及氧化谷胱甘肽(GSSG)的增加。α -生育酚和gsh缺乏症均可增强红细胞对氧化膜损伤的敏感性,降低热影响红细胞的变形能力。在热皮肤损伤后立即给予α -生育酚(20 ml/kg b.m),可防止红细胞维生素E减少和过氧化膜损伤,并改善其变形能力。这些结果有力地证明,红细胞变形能力下降与烧伤后早期红细胞α -生育酚缺乏和氧化膜损伤有关。
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引用次数: 0
Influence of aluminium on erythropoiesis, iron metabolism and some functional characteristics of erythrocytes in rats. 铝对大鼠红细胞生成、铁代谢及红细胞某些功能特性的影响。
T Ganchev, E Dyankov, R Zacharieva, I Pachalieva, M Velikova, B Kavaldjieva

The increased aluminium (Al) levels in serum of patients with chronic renal failure on hemodialysis are associated with impaired erythropoiesis and iron metabolism. The long term Al loading of rats (20 to 90 days) has similar effect. Data are still lacking about the effects after short-term aluminium treatment. The 7 day's treatment with Al2(SO4)3 in a dose 67.5 mg/kg b. w., i. m. m. significantly decreased hemoglobin, hematocrit, incorporation of 59Fe in newly formed erythrocytes and increased reticulocytes in absolute and relative counts. We observed a mild degree hypochromic, ferropenic, microcytic anemia and polychromazia in the available macrocytes. The immature erythroblasts were predominant forms in the erythroblastogram while the number of mature erythroblasts was decreased. Index of maturation of erythroblasts was lower, indicating inhibited erythroblast maturation. Plasma iron, TIBC, transferrin saturation and 59Fe absorption in the experimental group were significantly decreased. Spontaneous and mechanical hemolysis of erythrocytes were lower while erythrocyte deformability was increased. Obviously, Al treatment inhibits erythropoiesis and iron metabolism, probably hinders hemoglobin synthesis and erythroid cell maturation but does not affect the studied functional characteristics of mature erythrocytes negatively.

慢性肾功能衰竭血液透析患者血清铝(Al)水平升高与红细胞生成和铁代谢受损有关。大鼠长期负荷量(20 ~ 90天)也有类似效果。短期铝治疗后的效果仍缺乏数据。Al2(SO4)3 (67.5 mg/kg体重)处理7 d后,显著降低血红蛋白、红细胞压积、新形成红细胞中59Fe的掺入,增加网织红细胞的绝对和相对数量。我们观察到在可用的大细胞中有轻度的低色、缺铁、小细胞贫血和多色。未成熟的红母细胞在成红细胞图中占主导地位,成熟的红母细胞数量减少。红母细胞成熟指数降低,表明红母细胞成熟受到抑制。实验组血浆铁、TIBC、转铁蛋白饱和度和59Fe吸收率均显著降低。红细胞自发溶血和机械溶血降低,红细胞变形能力增强。显然,Al处理抑制了红细胞生成和铁代谢,可能阻碍了血红蛋白合成和红细胞成熟,但对成熟红细胞的功能特征没有负面影响。
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引用次数: 0
Behavioral changes as a result of dotarizine or flunarizine influence on dopaminergic neurotransmission in the striatum. 多他嗪或氟桂利嗪对纹状体多巴胺能神经传递的影响所导致的行为改变。
V D Petkov, B Petkova

In experiments on rats, we studied the changes in stereotypy induced by apomorphine (2.5 mg/kg i.p.) or amphetamine (2 mg/kg i.p.) and in haloperidol (1 mg/kg i.p.) catalepsy in rats treated with dotarizine (25 mg/kg orally), flunarizine (25 mg/kg) or vehicle for 10 days. Dotarizine did not induce any significant changes in the intensity and duration of apomorphine- or amphetamine-induced stereotypy nor in haloperidol-induced catalepsy. The flunarizine-induced changes in the behavioral effects of apomorphine, amphetamine and haloperidol suggest the decrease of striatal dopaminergic neurotransmission, whereby the risk of occurrence of extrapyramidal side effects of the drug when used in clinical practice. Dotarizine is not associated with such a risk.

在大鼠实验中,我们研究了阿波啡(2.5 mg/kg i.p)或安非他明(2 mg/kg i.p)和氟哌啶醇(1 mg/kg i.p)对多他嗪(25 mg/kg口服)、氟桂利嗪(25 mg/kg口服)或载药治疗10天大鼠的刻板印象的变化。Dotarizine在阿波啡或安非他明诱导的刻板印象的强度和持续时间以及氟哌啶醇诱导的猝睡中没有引起任何显著变化。氟桂利嗪引起的阿波啡、安非他明和氟哌啶醇行为效应的改变提示纹状体多巴胺能神经传递减少,从而在临床应用时增加了该药发生锥体外系副作用的风险。Dotarizine与这种风险无关。
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引用次数: 0
Perceptual grouping of strip dot patterns. 条形网点图案的感知分组。
N Bocheva, N Yakimoff, P Vos

Grouping of one-dimensional (strip) dot patterns was investigated, using an adjustment procedure to evaluate the distance (adjusted gap) at which two patterns appear to merge in a single strip. The size of the patterns had only a scaling effect on the adjusted gap. The adjusted gap and the variance of the estimates were influenced by the number of dots and the regularity (similarity, symmetry) of the patterns in the pair. Models of proximal grouping failed to account for the results obtained. A two-stage process implying determination of dot location and evaluation of inter-dot separation by means of "eclectic units" (Morgan, Hole & Glennerster, 1990) was considered to explain the findings.

研究了一维(条形)网点图案的分组,采用一种调整程序来评估两个图案在单个条带中合并的距离(调整间隙)。图案的大小对调整后的间隙只有比例效应。调整后的间距和估计的方差受点的数量和对中图案的规律性(相似性,对称性)的影响。近端分组模型未能解释所获得的结果。通过“折衷单位”(Morgan, Hole & Glennerster, 1990)确定网点位置和评价网点间分离的两阶段过程被认为可以解释这一发现。
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引用次数: 0
Altered response characteristics of cat visual neurons after systemic administration of the dihydropyridine calcium antagonist nimodipine. 全身给予二氢吡啶钙拮抗剂尼莫地平后猫视觉神经元反应特性的改变。
H J Koch

Nimodipine, a cerebrovasotropic dihydropyridine calcium antagonist, has gained increasing interest in geriatric research during last years and is discussed with regard to its possible involvement in restoration and preservation of brain plasticity. Single unit responses were recorded by microelectrodes in the visual cortex of anaesthetized adult cats. Receptive fields were stimulated with light bars moved forward and backward or flashed On/Off. Neuronal activity was recorded before and 5 and 30 min after i.v. administration of 0.1 mg/kg nimodipine. On the basis of penstimulus-time-histograms (PSTH) the response was analysed. There was a marked variability of the response after stimulation with both stationary and moving bars. Median firing rate was reduced 5 min after injection following On-stimulation but generally rose 30 min both after stimulation with light bars flashed On or Off Following stimulation with moving light bars about 60% of neurons showed decreased firing rates and 40% of neurons increased firing rates after injection of the calcium antagonist. The latency following On/Off-stimulation was rather constant, whereas the median latency following stimulation with moving light bars increased by about 15O ms after administration of nimodipine. In conclusion, nimodipine alters neuronal response characteristics in the visual cortex of the cat.

尼莫地平是一种有利于脑血管的二氢吡啶钙拮抗剂,近年来在老年研究中引起了越来越多的兴趣,并讨论了其在恢复和保存大脑可塑性方面的可能参与。用微电极在麻醉的成年猫的视觉皮层记录单单位反应。感受野被前后移动的光条或闪烁的开/关刺激。记录尼莫地平0.1 mg/kg静脉滴注前、5 min和30 min后神经元活动。在脉冲刺激-时间直方图(PSTH)的基础上分析了响应。在固定杆和移动杆刺激后,反应有明显的可变性。注射钙拮抗剂后,中位放电率在开启刺激后5分钟降低,但在开启或关闭光条刺激后30分钟普遍升高。在移动光条刺激后,约60%的神经元放电率降低,40%的神经元放电率升高。打开/关闭刺激后的潜伏期相当稳定,而移动光条刺激后的中位潜伏期在给予尼莫地平后增加了约15O ms。综上所述,尼莫地平改变了猫视觉皮层的神经元反应特征。
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引用次数: 0
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Acta physiologica et pharmacologica Bulgarica
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