ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.538302000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

In isolated rat soleus muscle an average of 23% of the total22Na influx was found to be suppressible by bumetanide (K0.5=0.1 mm) and furosemide (K0.5=1 mm), whereas the influx and efflux of42K were not affected. In extensor digitorum longus muscle, around 25% of the total22Na influx was suppressible by bumetanide (1 mm). In the presence of ouabain, both diuretics decreased net intracellular accumulation of Na+, but caused no change in K+content. In extensor digitorum longus (but not in soleus), bumetanide‐suppressible22Na influx was stimulated by increasing extracellular osmolarity with the bumetanide having no effect on42K influx. Bumetanide‐suppressible Na+influx was almost abolished in Cl‐‐free buffer, but was unaffected by the omission of K+. In rat soleus, the inhibitory effects of bumetanide, amiloride and tetrodotoxin on22Na influx were found to be additive. The results indicate that a NaCl cotransport system is present in both fast‐ and slow‐twitch skeletal muscles, and may participate in volume regulation. Due to the large pool of muscle cells, activation of NaKCl2cotransport is likely to entail the hazards of hypokalemia. The advantage of exerting volume control via NaCl cotransport is that this risk can

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.542296000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

Although endurance training enhances the antioxidant defence of different tissues, information on the effect of sprint training is scanty. We examined the effect of sprint training on rat skeletal muscle and heart antioxidant defences. Male Wistar rats, 16–17 weeks old, were sprint trained on a treadmill for 6 weeks. Total glutathione levels and activities of glutathione peroxidase, glutathione reductase, glutathione S‐transferase and superoxide dismutase in heart and various skeletal muscles were compared in trained and control sedentary animals. Lactate dehydrogenase and citrate synthase enzyme activities were measured in muscle to test the effects of training on glycolytic and oxidative metabolism. Sprint training significantly increased lactate dehydrogenase activity in predominantly fast glycolytic muscles and enhanced total glutathione contents of the superficial white quadriceps femoris, mixed gastrocnemius and fast‐glycolytic extensor digitorum longus muscles. Oxidative metabolic capacity increased in plantaris muscle only. Compared with the control group, glutathione peroxidase activities in gastrocnemius, extensor digitorum longus muscles and heart also increased in sprint trained rats. Glutathione reductase activities increased significantly in the extensor digitorum longus muscle and heart. Glutathione S‐transferase activity was also higher in the sprint trained extensor digitorum longus muscle. Sprint training did not influence glutathione levels or glutathione‐related enzymes in the soleus muscle. Superoxide dismutase activity remained unchanged in skeletal muscle and heart. Sprint training selectively enhanced tissue antioxidant defences by increasing skeletal muscle glutathione content and upregulating glutathione redox cycle enzyme activities in fast and mixed fibre leg muscles

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.540305000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

We have studied the importance of tachykinins and acetylcholine for motor stimulation of the rat duodenumin vitro. Contractions induced by transmural nerve stimulation and tachykinin receptor agonists selective for NK1, NK2 and NK3 receptors were used in combination with a neurokinin (NK)2 receptor antagonist, MEN 10,627, and atropine as a muscarinic receptor antagonist. Transmural nerve stimulation in the range 0.5–32 Hz caused frequency‐dependent contractions. MEN 10,627 (10‐8, 10‐7and 10‐6m) dose‐dependently reduced the contractile frequency–response curve (P<0.01–0.001). Addition of atropine (10‐6m) completely inhibited the response to transmural nerve stimulation (P<0.001). As control, atropine alone reduced this response only by about 65%. Of the tachykinin analogues, [β‐Ala8]‐neurokinin A(4‐10) selective for NK2 receptors caused concentration‐dependent contractions with high potency (pD28.01) and high efficacy, while substance P methyl ester acting on NK1 receptors had lower potency (pD27.94) and low efficacy, and senktide acting on NK3 receptors had a low potency (pD27.52) but high efficacy. With increasing concentrations of MEN 10,627 the response to [β‐Ala8]‐neurokinin A(4‐10) was markedly reduced (P<0.01), while responses to substance P methyl ester and senktide were only slightly affected. Our results indicate that the physiological contractile responses of the rat duodenum are co‐mediated by acetylcholine and tachykinins, for which NK2

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.539297000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The mechanism of electrical restitution was studied in isolated rat ventricular muscle using drugs that inhibit specific ion currents. The effect of transient changes in cytosolic Ca concentration and Na/Ca exchange in relation to the restitution process was also studied in single ventricular cardiomyocytes. Conventional microelectrode techniques were applied to record action potentials having gradually increasing coupling intervals, each evoked following a train of stimuli with a frequency of 1 Hz. Ion currents were recorded from enzymatically isolated cells using the whole cell patch clamp technique. Ca transients were monitored in myocytes loaded with the fluorescent dye, indo‐1. The electrical restitution process in multicellular rat ventricular preparations at 37 °C was described as a sum of three exponential components: an early positive component, a subsequent fast negative component and a late negative component, having time constants of 21.9±1.9, 73.1±6.0 and 1053±61 ms, respectively (n=9). Inhibition of the transient outward K current, the delayed rectifier K current, or the chloride current did not substantially alter these time constants. The early positive and fast negative components were fully abolished by nifedipine or MnCl2. In the presence of caffeine, the fast negative component was absent, while the time constant of the early positive component increased to 39.5±5.8 ms (n=5). In single myocytes loaded with indo‐1, the Ca transients decayed with a time constant of 151±12 ms at room temperature (n=5). These Ca transients were accompanied by inward current tails, identified as a Na/Ca exchange current, having a decay time constant of 140±4.5 ms. It is concluded that electrical restitution in rat ventricular muscle is relatively little affected by recovery from voltage‐dependent inactivation of ion channels, it is rather governed by transient changes in cytosolic Ca concentration possibleviaCa‐dependent inactivation of the L‐type Ca current and activation of the Na/Ca

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.541304000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The effect of the immunosuppressant FK506 on ischaemic neuronal damage was studied in a rat model of transient cerebral ischemia induced by occlusion of both common carotid arteries in combination with hypotension for 10 min. Neuronal damage was assessed morphologically after 4 days of recovery. Treatment with FK506, given at a dose of 2 mg kg‐1by intraperitoneal injections 30 min prior to ischemia and once daily during recovery, decreased neuronal damage by 52% in the hippocampal CA1 region and by 48% in the temporal cortex. The protection was not due to diminished body temperature or a marked reduction of ischaemia‐induced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin‐mediated events or by preserving mitochondrial fun

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.535298000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The plasma volume (PV) decline upon 1.5, 3, 5, 8, 10, 15 and 35 min periods of quiet standing was studied (Hb/Hct) in male volunteers (n=7). This approach permitted detailed definition of the time‐course of the volume change. PV decreased by as much as 8.5±0.4% (328±15 mL) after 3 min standing and by no less than 11.7±0.4% (466±22 mL) after 5 min. The reduction was 14.3±0.7, 16.8±0.8, 17.7±0.8 and 17.4±0.9% after 8, 10, 15 and 35 min, or 568±30, 671±39, 707±41 and 691±44 mL. These data, in conjunction with the 1.5 min experiments, indicated a very rapid≈125 mL min‐1fluid loss initially on standing. However, the PV loss showed marked decline with time and was virtually completed within 10 min. Finally, the observation was made that the rate of PV recovery after standing was inversely related to the duration of standing. It is suggested that (a) the transcapillary hydraulic conductivity in the dependent limbs, the predominant targets for fluid filtration on standing, is about 0.010 mL min‐1100 mL‐1mmHg‐1and much greater than indicated previously. However, protective mechanisms restrict rapid fluid loss to early phases of standing. (b) Decrease in PV may contribute importantly to haemodynamic stress and to orthostatic, fainting reactions during short quiet standing. Apparently, PV loss may be equally important as pooling of blood, traditionally regarded as a dominant cause of adverse orthostatic reactions. (c) The duration of standing, as such, may be critical for the rate of PV

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.521294000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The genetically altered hypothalamo‐pituitary‐adrenocortical axis in the spontaneously hypertensive rat (SHR) suggests altered phagocyte function in this strain. We therefore compared luminol‐amplified chemiluminescence in peritoneal leucocytes from 10‐ to 12‐week‐old SHRs and age‐matched Wistar–Kyoto rats (WKYs) activated by serum‐opsonized zymosan particles (SOZ),N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (fMLP) or phorbol 12‐myristate 13‐acetate (PMA). While the number of peritoneal monocytes/macrophages was increased by 49% in SHRs relative to WKYs, activator‐induced chemiluminescence per cell in SHRs was only 14–42% of that in WKYs. FMLP responses were especially low in SHRs. Treatment of rats with dexamethasone in the drinking water for 48 h prior toex vivoexperiments reduced chemiluminescence dose‐dependently in WKYs as well as in SHRs. ED50of dexamethasone in SHRs was, however, increased compared to WKYs, indicating lowered sensitivity to dexamethasone in SHRs. No evidence was found of strain differences in differential distribution of peritoneal cells or in pharmacokinetics of dexamethasone. Plasma ACTH levels were significantly higher in SHRs than in WKYs, while basal plasma corticosterone concentrations in SHRs and WKYs were not significantly different. The results suggest that production of reactive oxygen compounds by peritoneal mononuclear phagocytes is reduced in SHRs compared with WKYs, and that the phagocyte respiratory burst is modulated differently by endogenous glucocorticoids in the two strains. We propose that reduced activity of the phagocyte NADPH oxidase‐myeloperoxidase system is a major contributory cause of the altered chemiluminescence responses in SHRs. The data indicate that species differences may also be present at earlier steps in the signal transduct

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.622299000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The anterior cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from synovial fluid. In order to quantitate the relative importance of these two routes and to compare the anterior cruciate ligament with the medial collateral ligament, we injected [3H]methyl‐glucose as a tracer intravenously or directly into the knee in rabbits. Tracer concentrations in plasma, synovial fluid, the anterior cruciate ligament and the medial collateral ligament were analysed by a pharmacokinetic compartment model developed for this study. The contribution of [3H]methyl‐glucose permeation from the synovial fluid was calculated at 59.7% in the anterior cruciate ligament and at 18.1% in the medial collateral ligament. We concluded from these results that the nutrition for the medial collateral ligament, which is an extraarticular structure, is provided mainly by its vascular supply. In contrast, synovial fluid permeation is an important transport route for small molecules for the normal anterior cruciate ligam

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.537301000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY

摘要:

The non‐peptide ET‐receptor antagonist Bosentan was used to investigate the role of endogenous endothelin‐1 (ET‐1) in the development of the Sephadex‐induced lung inflammation in the rat. Intratracheal instillation of Sephadex caused a 60‐fold rise in endothelin‐1‐like‐immunoreactivity (ET‐1‐LI) in bronchoalveolar lavage fluid (BALF) concomitant with development of lung oedema, an influx of inflammatory cells into the airways and a rise in the protein content in BALF. The ET‐1‐LI level in lung homogenate was not significantly affected. Pre‐treatment with Bosentan reduced ET‐1‐LI content in the lung parenchyma but increased ET‐1‐LI levels in BALF, possibly indicating an effective displacement of ET‐1 from its receptors. In Bosentan‐treated animals there was an enhancement of the lung oedema formation following Sephadex instillation, but no significant change in the number of leucocytes or protein concentration in BALF. The present data thus do not support the hypothesis that endogenous ET‐1 mediates oedema formation or leucocyte influx in this model. If anything, Bosentan enhanced the oedema formation i

ISSN:0001-6772    

DOI:10.1046/j.1365-201X.1996.543303000.x

出版商:Blackwell Science    

年代:1996

数据来源: WILEY