bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of reperfusion-induced ventricular arrhythmias in isolated rat heart with magnesium
Authors: Bril Antoine , Rochette Luc
Published: April 2011

The effects of magnesium (from 1.2 to 7.2 mM) were investigated in isolated perfused rat heart subjected to coronary artery ligation and reperfusion. Increasing magnesium concentrations, of the medium containing 3.00 mM of calcium, induced a significant bradycardia and a protective effect towards reperfusion arrhythmias. A significant correlation was found between the heart rate and the antiarrhythmic activity of increasing magnesium concentrations. The effects of high magnesium concentration (4.8 mM) were also investigated after labelling of internal stores of noradrenaline with [3H]noradrenaline. Without any marked change in the pattern of release of radioactivity, a significant reduction of the sudden release of radioactivity was observed during the reperfusion. However, magnesium did not change the uptake of noradrenaline by the heart. Our results suggest that the antiarrhythmic effect of magnesium might be of importance in the clinical treatment of myocardial ischemia.Key words: magnesium, isolated rat heart, reperfusion, arrhythmias, noradrenaline.
The effects of temperature on contractile mechanisms of rainbow trout (Salmo gairdneri) intestine
Authors: Burka John F. , Briand Heather A. , Blair Rosalind M. J. , Purcell Lisa M. , Calder Gillian F.
Published: April 2011

Experiments were designed to determine whether contractility of trout smooth muscle in vitro varied with temperature and if changes occurred at the receptor or intracellular levels. The role of calcium in contractility at various temperatures was also investigated. Isolated trout intestinal segments, approximately 2 cm in length, were suspended isometrically under 2 g tension in 10-mL organ baths containing trout Ringer's solution aerated with O2 and CO2 (95:5). Contractions of trout intestine were not statistically different at 10 and 20 °C for carbachol, 5-hydroxytryptamine, and KCl. However, the efficacy, but not the potency, of each agonist was decreased at 2 °C. Receptor-induced contractions were reduced to a greater extent at 2 °C and did not recover to the same extent when returned to 10 °C in comparison with those induced by depolarization. The calcium source for contractility was also dependent on temperature. As temperatures increased, utilization of intracellular calcium increased, as indicated by increased contractility in the absence of extracellular calcium. Thus, low temperatures decrease smooth muscle contractility by affecting receptor-mediated events rather than the intracellular contractile mechanisms. Receptor-operated agonists appear to have a higher capability of using intracellular calcium than depolarizing agents.Key words: trout, intestine, smooth muscle, calcium, temperature, 5-hydroxytryptamine, muscarinic receptors, potassium.
Characterization of the high and low affinity components of the renal Ca2+ – Mg2+ ATPase
Authors: Brunette M. G. , Mailloux J. , Chan M. , Ramachandran C.
Published: April 2011

The purpose of this study was to characterize the interrelationship between free calcium (Ca2+) and magnesium (Mg2+) in the Ca2+ ATPase enzyme cycle of kidney membranes. Experiments were performed with basolateral membranes from rat renal cortex and microdissected proximal and distal tubules from mice. Results were similar in the three types of preparations. We first investigated the effect of ATP concentration on Ca2+- and Mg2+-dependent ATP hydrolysis. With 0.2 μM Ca2+, the enzyme activity, as a function of ATP concentration, showed two saturable components: a high affinity component with a Km of 33 μM ATP and a low affinity component with a Km of 0.63 mM ATP. These components may represent either two distinct sites of ATP binding or two forms of the same site. For the sake of simplicity, it was assumed that the two components correspond to a high affinity and a low affinity substrate site. At the high affinity site (ATP = 50 μM), the Ca2+ dependence of ATP hydrolysis followed a single Michaelis–Menten kinetics with Km for Ca2+ of 0.08 μM. The addition of 1 mM Mg2+ resulted in a relatively constant increase in ATP hydrolysis at all Ca2+ concentrations, indicating that the effects of the two cations were additive. With high ATP concentration (ATP = 3 mM), Ca2+ also induced an ATP hydrolysis according to a saturable process, with a Km for Ca2+ of 0.2 μM. In contrast with what occurred with low concentrations of ATP, addition of millimolar Mg2+ completely curtailed the sensitivity of the enzyme to Ca2+. However, traces of Mg2+ (< 10−6 M), while decreasing the Vmax of the Ca2+ ATPase, increased the affinity of the enzyme for Ca2+. These results indicate that with high concentrations of ATP, Mg2+ not only modifies the enzyme conformation but also displaces Ca2+. The effects of calmodulin, vanadate, and lanthanum were also examined using low and high concentrations of ATP. With 50 μM ATP, neither 0.5 μM calmodulin nor 100 μM lanthanum had any influence on the Ca2+-dependent ATP hydrolysis; in contrast, 100 μM vanadate significantly diminished the enzyme activity. With 3 mM ATP, 0.5 μM calmodulin increased the affinity of the enzyme for Ca2+, whereas 100 μM vanadate decreased it. These results suggest that the effect of calmodulin occurs only when the two sites are occupied, whereas vanadate interferes in presence of both low and high ATP concentrations. Based on the analogy with the sequential elementary steps described for other membrane Ca2+ ATPases and for Na+–K+ ATPase, and on the similarities between these characteristics of ATP hydrolysis and those of the enzyme phosphorylation on one hand and ATP-dependent Ca2+ transport on the other hand, we propose that the phosphoenzyme formation occurs at the high affinity site and that Ca2+ transport is directly related to ATP binding at the low affinity site, which might be considered as a regulatory site.Key words: kidney Ca2+ ATPase, ATP magnesium and calcium on Ca2+ ATPase, ATP-dependent calcium transport in kidney.
Renal synthesis of epidermal growth factor is unchanged by vitamin D deficiency
Authors: Goodyer Paul R. , Langshur Sharon , Fata Jehane
Published: April 2011

In mammalian kidney, epidermal growth factor (EGF) is produced as a small internal domain of an abundant high molecular weight peptide associated with the luminal membrane of the thick ascending limb of Henle's loop and distal convoluted tubule. At present, there is no evidence to indicate a mitogenic function for the EGF-containing molecule in kidney; consideration of its molecular structure suggests the possibility of a membrane-associated physiologic role. In this study, we examine regulation of renal EGF synthesis during induction of vitamin D deficiency in mice. Despite evidence of marked hyperparathyroidism, urinary excretion of EGF was equivalent in control (2.54 ± 0.72 μg/mg creatinine) and vitamin D deficient (2.13 ± 0.97 μg/mg creatinine) animals. Similarly, EGF mRNA levels in kidney were comparable in the two groups. These data indicate that parathyroid hormone has no effect on renal EGF regulation, although it is known to stimulate calcium reabsorption in distal nephron segments.Key words: epidermal growth factor, vitamin D, calcium, kidney, parathyroid hormone.
Effect of human plasma proteins on spontaneous contractile activity of rat mesenteric portal vein
Authors: Pillai G. , Sutter M. C.
Published: April 2011

This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, γ-globulin, α-globulin, β-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the γ-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or γ-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to α-globulin or α - and β-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of γ-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by γ-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on α-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension.Key words: vasomotion, mesenteric portal vein, plasma proteins, albumin, γ-globulin, inhibitory factor, stimulatory factor, IgG.
Effects of taurine depletion on intrinsic contractility of rat ventricular papillary muscles
Authors: Lake N. , Splawinski J. B. , Juneau C. , Rouleau J. L.
Published: April 2011

Contractile parameters in Krebs–Henseleit media containing various calcium concentrations were compared in left ventricular papillary muscles of two groups of rats: control and taurine depleted. All tests were carried out with the muscles at initial length, Lmax, the length that produced maximal active tension. From measurements of after- and un-loaded contractions, the velocity–tension curves and the derived maximum velocity of shortening were not different between the groups. Time to peak shortening and extent of shortening were not altered, while relaxation times and contraction duration were significantly prolonged for taurine-depleted muscles. Peak isometric tension and its rate of development were significantly reduced in taurine-depleted muscles compared with controls. Postrest (3 min) stimuli and paired stimuli (200-ms interval) evoked similar potentiated contractile responses in both groups, such that the ratio of their peak tensions remained unchanged. For taurine-depleted muscles the force-frequency relationship (a negative staircase) was parallel to, but lower than, control. These experiments suggest that taurine deficiency leads to reductions in action potential triggered calcium release from internal stores, and deficits in calcium sequestration. This may result from disfacilitation of calcium binding to the sarcoplasmic reticulum and other storage sites during taurine deficiency.Key words: taurine depletion, rat papillary muscle contractility.
A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit
Authors: Kappagoda C. Tissa , Thomson Alan B. R. , Senaratne Manohara P. J.
Published: April 2011

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (−9.0 to −5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (−6.0 log mol/L) was significantly (p < 0.05) impaired in the experimental group (34.3 ± 3.8%) compared with that in the control group (79.8 ± 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 ± 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 ± 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.Key words: atherosclerosis, endothelium-dependent relaxation, rabbit aorta, regression.
Coronary vasodilation caused by intravenous cocaine in the anesthetized beagle
Authors: Friedrichs Gregory S. , Wei Hwu-Meei , Merrill Gary F.
Published: April 2011

The aim of this study was to determine the effect of intravenous cocaine on the coronary circulation in the dog. Sixteen beagles separated into three groups were administered either cocaine (n = 8) or lidocaine (n = 4) at doses of 0.4, 2.0, and 10.0 mg/kg under conditions of constant coronary blood flow. A third group of beagles (n = 4) was administered cocaine under conditions of natural coronary blood flow. In the first group, the lowest dose of cocaine had no significant effect on coronary perfusion pressure, even though it increased mean systemic arterial pressure by 10% (p < 0.05). The second two doses decreased coronary perfusion pressure by 13 (p < 0.05) and 68% (p < 0.05), respectively. In the second group, the lowest dose of lidocaine did not significantly affect coronary perfusion pressure. However, the second two doses significantly decreased coronary perfusion pressure by 22 (p < 0.05) and 45% (p < 0.05), respectively. Under conditions of natural coronary blood flow and coronary perfusion pressure, these same doses of cocaine increased coronary blood flow by 25, 63, and 175%, respectively. All coronary vascular responses occurred 60 s after administration of cocaine or lidocaine. We conclude that cocaine causes rapid, dose-dependent coronary vasodilation in the anesthetized beagle. The coronary vasodilation appears to be related to cocaine's known, local anesthetic properties.Key words: constant flow, vasodepressor, lidocaine, local anesthetic, myocardium.
Myosin phosphorylation, twitch potentiation, and fatigue in human skeletal muscle
Authors: Houston Michael E. , Grange R. W.
Published: April 2011

Twitch tension and phosphate incorporation into the phosphorylatable light chains (P-light chains) of myosin were studied during a 10-min recovery period following a 10- or 60-s maximal voluntary isometric contraction (MVC) in 18 subjects. Analysis of muscle biopsy samples obtained before, immediately after, 1 min, and 10 min following the 10-s MVC revealed that the 10-s MVC produced a modest but transient metabolic displacement from rest, a 35% decrease in phosphocreatine, and a threefold elevation in lactate concentration. Immediately after the 60-s MVC, ATP was decreased by 20%, phosphocreatine decreased by 84%, and lactate was elevated by 15-fold. Lactate remained elevated over the 10-min recovery period. Twitch force was maximally potentiated following the 10-s MVC and declined to rest by 10 min of recovery. Twitch force was 0.66 of rest value immediately after the 60-s MVC, then increased over the next 4 min to reach a potentiated value 21% greater than rest, before declining. Significant phosphate incorporation into P-light chains was observed immediately after both contractions, but dephosphorylation to rest values at the end of recovery was only noted for the 60-s condition. These results demonstrate an inconsistent relationship between twitch tension enhancement and P-light chain phosphorylation in the in vivo human model.Key words: myosin phosphorylation, human muscle, metabolism, fatigue.
Use of deuterated water for measurement of short-term cholesterol synthesis in humans
Authors: Jones Peter J. H.
Published: April 2011

Previous methods for measurement of cholesterol synthesis de novo in humans have either required extended measurement periods or been indirect. Recently, a technique based on the rate of incorporation of deuterium from D2O into the plasma cholesterol pool has been developed. Following oral ingestion of D2O, deuterium enrichment over time in free plasma cholesterol after combustion and reduction was determined using isotope ratio mass spectrometry. This methodology enabled direct measurement of plasma cholesterol synthesis over intervals as short as 4 h. The technique has been used to demonstrate changes in synthetic rate in response to feeding conditions and genetic influences. Fasting over 36 h resulted in markedly reduced deuterium uptake into cholesterol in healthy males. Diurnal variations in synthetic rate have also been identified, with elevated synthesis observed during nocturnal periods in both fed and fasted subjects. In addition, the influence of apolipoprotein E phenotype on cholesterol synthesis has been shown using this technique. Individuals carrying the apoprotein ε2 allele demonstrated lower synthesis compared with those possessing the ε4 allele. Thus, the deuterium incorporation technique for measuring cholesterol synthesis demonstrates potential as a valuable stable isotope method for human nutrition studies.Key words: cholesterol synthesis, human, deuterium, methodology.
Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: effects of serotonin, substance P, and thyrotropin-releasing hormone
Authors: Backman S. B. , Sequeira-Martinho H. , Henry J. L.
Published: April 2011

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8–T10 in the cat were compared according to their responses to iontophoretic application of serotonin, substance P, and thyrotropin-releasing hormone (TRH). Responses of both types of SPN to iontophoretic application of serotonin were characterized by an increase in the rate of discharge that was slow in onset (mean ± SD = 36 ± 21 s) and prolonged in afterdischarge (115 ± 70 s) following termination of application. Depression was never observed and responses were similar whether using serotonin at a pH of 3.3 or 4.5, suggesting that the absence of a depressant effect cannot be accounted for by pH, as has been reported with cortical neurones. Iontophoretic application of methysergide resulted in a decrease in the rate of discharge of both types of SPN and blocked the excitatory responses to serotonin. Adrenal and nonadrenal SPNs were excited by iontophoretic application of substance P. Responses of both types of SPN were similar and were characterized by a gradual increase in the rate of discharge that was slow in onset (42 ± 27 s) and prolonged in afterdischarge (96 ± 42 s). Finally, adrenal and nonadrenal SPNs were also weakly excited by iontophoretic application of TRH. These responses were slow in onset (48 ± 27 s) and prolonged in afterdischarge (78 ± 35 s). These data indicate that serotonin, substance P, and TRH exert excitatory effects on functionally dissimilar sympathetic preganglionic neurones and support the possibility that they may be chemical mediators of synaptic transmission in the intermediolaterai nucleus. In addition, these data may be interpreted to support the notion that serotonin, substance P, and TRH are involved in global activation of the sympathetic nervous system.Key words: sympathetic preganglionic neurone, spinal cord, lateral horn, iontophoresis, serotonin, substance P, thyrotropin-releasing hormone.
Oxygen and substrate deprivation on isolated rat cardiac myocytes: temporal relationship between electromechanical and biochemical consequences
Authors: Fantini Elisabeth , Athias Pierre , Courtois Martine , Khatami Shorheh , Grynberg Alain , Chevalier Annick
Published: April 2011

The effects of hypoxia and reoxygenation on action potentials (AP), contractions, and certain biochemical parameters were studied in isolated rat ventricular myocytes in monolayer culture in the presence and absence of glucose. Substrate deprivation alone had no influence on the basal properties. In the presence of glucose, a 4-h hypoxic treatment caused only a moderate decrease in AP amplitude and rate. In substrate-free conditions, hypoxia induced a gradual decline in plateau potential level and in AP duration and rate, followed by rhythm abnormalities and a failure of the electromechanical coupling. Spontaneous AP generation then ceased, and the resting potential decreased with increased duration of hypoxia. These alterations were associated with a decrease in ATP content, an increase in the lactate production, and a leakage of about 50% of the total cellular lactate dehydrogenase (LDH). Cells reoxygenated after 150 min hypoxia recovered near-normal function, while the ATP depletion ceased and the rate of lactate and LDH loss was diminished. Conversely, cells reoxygenated after 4 h hypoxia exhibited a further decrease of the residual resting polarization and no change in the decline of intracellular ATP and in the efflux of cytosolic lactate and LDH. The results of this study indicate that (1) the sequence and the extent of functional alterations are dependent on the duration of hypoxia in the absence of exogenous substrate and (2) ATP depletion and the amount of lactate and LDH released during hypoxia are related to the shift from reversibly to irreversibly damaged cells.Key words: cultured rat cardiomyocytes, electromechanical properties, hypoxia–reoxygenation, glucose deprivation, enzyme release.
Reversible elimination of myofibrillar Ca2+ sensitivity by diamide and other sulfhydryl reagents: comparison with reversible contracture produced in intact cells
Authors: Gailis Laimonis , Nayler Winifred G. , Harding Sian E.
Published: April 2011

Cardiac contractile activity is usually controlled by intracellular Ca2+, but it can also be modified by oxidizing agents. Incubation of guinea pig heart myofibrils with diamide (3 mM, 1 h) increased basal (no Ca2+) ATPase activity by 580% and abolished Ca2+ dependence. The effect was proportional to diamide concentration (0.01 – 1 mM) and duration of preincubation (up to 2 h). Dithiothreitol (5 mM, 1 h) reversed most of the basal ATPase activation and restored Ca2+ sensitivity. Other sulfhydryl reagents produced a similar effect but also produced inhibition of total ATPase. In intact cell preparations, diamide produced a slow tonic contraction, consistent with myofibril activation. In the perfused rat heart, 1 mM diamide slowly increased diastolic ventricular pressure; this increase was partially reversed by dithioerythritol. In isolated rat heart myocytes, 1 mM diamide produced a slow tonic contraction, increased contractility in response to stimulation. Cardiocytes superfused for 1 h with buffer containing EGTA to deplete Ca2+ did not contract in response to stimulation but showed a slow tonic contraction with diamide. This contraction could be slowly and only partially reversed by dithioerythritol. Response to stimulation was restored by addition of Ca2+. The results show that diamide can produce contraction in viable cells. This contraction does not require extracellular Ca2+ and is unlikely to involve intracellular Ca2+. The direct activation of myofibrillar ATPase may contribute to the increased myocardial stiffness seen in ischemia and to ischemic contracture.Key words: heart myofibril ATPase, calcium dependence, oxidizing agents, contracture.
Influence of exogenous fatty acids and ketone bodies on rates of lipolysis in isolated ventricular myocytes from normal and diabetic rats
Authors: Larsen Terje S. , Severson David L.
Published: April 2011

The effect of oleate (0.3 and 1.2 mM) and the combined effect of β-hydroxybutyrate (4 and 8 mM) and acetoacetate (1 and 2 mM) on rates of lipolysis (glycerol output) was determined with calcium-tolerant myocytes isolated from the hearts of normal rats and hearts from acutely (2–3 days; 100 mg/kg streptozotocin) diabetic rats. In addition, the effect of these exogenous substrates on rates of lipolysis was investigated in triacylglycerol (TG) loaded myocytes prepared from normal hearts by inclusion of oleate in the isolation solutions. Diabetic and TG-loaded myocytes had higher lipolytic rates than normal myocytes. In control myocytes, oleate (1.2 mM) did not affect basal lipolysis, but it reduced isoproterenol-stimulated lipolysis by 30%. In diabetic and TG-loaded myocytes, the addition of 1.2 mM oleate inhibited basal rates of lipolysis by 41 and 40%, respectively, and isoproterenol-stimulated rates of lipolysis by 43 and 53%, respectively. However, lipolytic rates measured in the presence of 1.2 mM oleate with diabetic and TG-loaded myocytes were still higher than lipolysis in normal myocytes incubated in the absence of oleate. Ketone bodies increased both basal and isoproterenol-stimulated lipolysis in normal myocytes. In diabetic myocytes, ketone bodies produced a modest stimulation of basal lipolysis but had no effect on isoproterenol-stimulated rates of lipolysis. These data indicate that mobilization of endogenous TG may play an important role in supplying energy to the heart in the diabetic state. Moreover, accumulation of endogenous TG in diabetic myocardium can only partly be explained by inhibition of lipolysis by exogenous substrates.Key words: lipolysis, cardiac myocytes, diabetes.
Gastrointestinal blood flow in the opossum with special reference to the esophagus
Authors: Zijlstra Folkert G. , Hynna-Liepert Taimi T. , Dinda P. K. , Beck Ivan T. , Paterson William G.
Published: April 2011

The opossum esophagus, like that of the human, is composed of striated muscle fibres proximally and smooth muscle fibres distally. Because of this similarity the opossum has been used extensively as an animal model for esophageal studies, but to date no data on esophageal blood flow have been reported in this species. The purpose of this study was to establish the basal blood flow characteristics of different regions of the opossum gastrointestinal tract with particular reference to the esophagus. Intracardiac injection of 15-μm microspheres was used to provide an estimate of blood flow (mL∙min−1∙g−1 dry tissue) to the whole wall, the combined layer of mucosa plus submucosa, and the muscularis propria. Basal blood flow in the whole tissue and mucosa–submucosa was significantly higher in the lower esophageal sphincter than in the proximal or distal esophagus. The muscularis propria blood flow displayed an aborally increasing gradient with flow to proximal esophagus (striated muscle) < distal esophagus (smooth muscle) < lower esophageal sphincter. Regional differences in blood flow to other regions of the gastrointestinal tract were similar to that described in other species. In addition, no changes in basal blood flow occurred despite repeated microsphere injections, suggesting that this species provides a good animal model for the study of gastrointestinal blood flow.Key words: microspheres, blood flow, esophagus, stomach, intestine.
Corticospinal control of soleus motoneurons in man
Authors: Advani A. , Ashby P.
Published: April 2011

Electrical or magnetic stimulation of the human motor cortex causes a strong, short latency facilitation of tibialis anterior (TA) motoneurons but only weak, longer latency changes in the excitability of soleus (SOL) motoneurons. The facilitation of TA motoneurons has been attributed to the monosynaptic action of the "fast" corticospinal pathway. The present study further investigates the cortical control of soleus motoneurons in man. In tests of reaction time to auditory stimuli, normal subjects took significantly longer to activate soleus motoneurons than tibialis anterior motoneurons. Thus we could not demonstrate the existence of a "fast" pathway from the brain to SOL motoneurons that, for some reason, is not activated by magnetic stimulation. The hypothesis that the cortex might control soleus motoneurons indirectly by modulation of the Ia input from muscle spindles was tested. Magnetic stimulation of the cortex was used to condition the facilitation of soleus motoneurons resulting from the stimulation of group I fibres in the tibial nerve. There were no consistent changes in Ia facilitation. We conclude (i) that there is no evidence so far that SOL motoneurons are excited by a direct pathway from the cortex (similar to that projecting to TA motoneurons) and (ii) that the observed changes in firing probability of soleus motoneurons produced by magnetic stimulation over the motor cortex do not result from modulation of presynaptic inhibition of Ia afferents.Key words: cortex, voluntary movement, magnetic stimulation.
Repeated amiodarone exposure in the rat: toxicity and effects on hepatic and extrahepatic monooxygenase activities
Authors: Daniels Jonathan M. , Leeder Randall G. , Brien James F. , Massey Thomas E.
Published: April 2011

Amiodarone is a potent and efficacious antiarrhythmic agent, yet associated with its use are life-threatening pulmonary fibrosis and hepatotoxicity. We have investigated the susceptibility of the male Sprague–Dawley rat to pulmonary and hepatic toxicity after repeated exposure to amiodarone and the effects of such exposure on hepatic and extrahepatic drug metabolizing enzymes. Animals received amiodarone (200 mg∙kg−1∙day−1 i.p., 5 days/week) for 1 week followed by 150 mg∙kg−1∙day−1 (5 days/week) for 3 additional weeks. No signs of pulmonary fibrosis or hepatotoxicity were observed, based on histological examination, lung hydroxyproline content, and plasma alanine aminotransferase activity. Analysis of tissues revealed extensive accumulation of amiodarone and desethylamiodarone in lung and liver, but concentrations were significantly lower in animals treated for 4 weeks than for 1 week. In a separate experiment, rats received amiodarone 150 mg∙kg−1∙day−1 i.p. (5 days/week) for 1 or 4 weeks. No differences in tissue concentrations of amiodarone and desethylamiodarone were detected between animals treated for 1 or 4 weeks. This regimen did not affect hepatic or extrahepatic monooxygenase activities. These results indicate that, in the male Sprague–Dawley rat, there is no observable pulmonary or hepatic toxicity following short-term amiodarone exposure, and there is enhanced elimination of amiodarone and desethyamiodarone when the daily dose of amiodarone is decreased after 1 week from 200 to 150 mg/kg.Key words: amiodarone, desethylamiodarone, pulmonary fibrosis, rat, lung.
Cyclic AMP effects on chloride transport and carbonic anhydrase activity in frog skin
Authors: Galar Ignacio , Marroquin Ma. del Carmen
Published: April 2011

Unidirectional (36Cl) chloride fluxes across isolated and short-circuited frog skin were measured, with both sides bathed in low chloride solution. Transepithelial chloride influx was inhibited by exogenous cAMP as well as by substances enhancing its cellular concentration, such as epinephrine, isoproterenol, and 3-isobutyl-1-methylxanthine (IBMX). Epinephrine and isoproterenol addition resulted in an increase of transepithelial chloride outflux, but exogenous cAMP or IBMX had no significant effect on this unidirectional flux. Phenylephrine had no significant effect on influx or outflux. Carbonic anhydrase (CA) activity in extracts obtained from frog skin epithelium was inhibited by pretreatment with IBMX at 4–5 °C and prolonged exposure to cAMP at freezing point. cAMP or IBMX alone had no significant effects on CA activity. This catalytic activity was chloride insensitive and was abolished by 0.1 μM. acetazolamide. Results suggest a [Formula: see text] exchange inhibition by cAMP via carbonic anhydrase inactivation. Chloride outflux stimulation by β-adrenergic agonists does not seem to depend solely on an increase in cAMP concentration.Key words: frog skin, chloride transport, exogenous and induced cAMP effects, carbonic anhydrase inhibition.
A physiological dose of estradiol with progesterone affects striatum biogenic amines
Authors: Morissette Marc , Lévesque Daniel , Bélanger Alain , Paolo Thérèse Di
Published: April 2011

The acute effect of estradiol and progesterone on dopamine and serotonin metabolism in rat striatum was studied. One subcutaneous injection of 17β-estradiol (300 ng) and progesterone (150 μg) into intact male rats increased plasma levels of these steroids, while testosterone, corticosterone, and estrone remained unchanged. Dehydroepiandrosterone, androstane-3β, 17β-diol and dihydrotestosterone remained undetectably low. Prolactin decreased and androstane-3α,17β-diol, and 17-OH progesterone increased, but less than estradiol and progesterone. Peak levels of striatal dopamine, dihydroxyphenylacetic acid, and homovanillic acid were observed 15–45 min after steroid injection with a return to control values after 45–60 min, while serotonin and 5-hydroxyindoleacetic acid levels were slightly decreased. An injection of estradiol (70 ng) with progesterone (70μg) to ovariectomized female rats left plasma prolactin levels unchanged, while striatum dopamine and serotonin as well as their metabolite concentrations peaked 15–60 min after steroid injection and returned to control values after 45–75 min. To allow for a better comparison of the action of these steroids, the effect of estradiol or progesterone alone and in combination on the brain of ovariectomized rats was compared in the same experiment. A similar increase in metabolites of dopamine levels was observed after these steroids alone or in combination, while dopamine levels were increased only after progesterone alone or in combination with estradiol. An injection of estradiol or progesterone to ovariectomized rats led to peak steroid concentrations at approximately the same time in the brain and plasma. In addition, plasma and brain steroid levels were significantly correlated. Thus, levels of estradiol and progesterone that occur during the estrous cycle can rapidly increase striatum dopaminergic activity in rats of both sexes, while serotonin activity is increased only in female rats.Key words: estradiol, progesterone, striatum, dopamine, serotonin.
Comparison of vascular response of different locations of the gastrointestinal tract to isoproterenol and nifedipine
Authors: Prokopiw I. , Dinda P. K. , Beck I. T.
Published: April 2011

In the present study we have compared the effect of intravenous infusion of a calcium channel blocker, nifedipine (1.0 μg∙kg−1∙min−1 for 20 min), with that of isoproterenol (0.1 μg∙kg−1∙min−1 for 20 min) on the hemodynamic parameters and the vascular response of different locations and tissue layers of the gastrointestinal tract. Heart rate increased with isoproterenol but not with nifedipine. Both agents caused a similar increase in cardiac output and a similar fall in mean arterial pressure. After 20 min infusion, nifedipine increased the blood flow of the axillary artery, but isoproterenol had no such effect. Isoproterenol caused vasodilation of the mucosa in the antrum but not in the fundus and the body of the stomach or in the duodenum, jejunum, mid small intestine, ileum, and colon. The mucosal effect of nifedipine was similar, except that it also caused vasodilation in the small bowel and in the ascending colon. Nifedipine caused vasodilation of the muscularis throughout the gastrointestinal tract, but isoproterenol had no such effect. These differences are discussed in relation to the mechanism of action of these two vasodilators. It is suggested that the vascular response of different locations and tissue layers of the gastrointestinal tract to vasodilators is locally regulated by a variety of mechanisms. These mechanisms may include β- and α-receptor density and (or) sensitivity, angiotensin II activity, and metabolic need of the tissues.Key words: nifedipine, isoproterenol, regional blood flow, microspheres, hemodynamics.
Determinants of atrial natriuretic factor secretion in dogs expanded with isotonic saline or colloid solutions
Authors: Cernacek Peter , Levy Mortimer
Published: April 2011

Though increments in blood volume and atrial pressure are thought to be the primary stimuli for ANF secretion, plasma levels of this peptide do not always behave as a simple function of volume status. To outline the relationship between the latter and cardiac ANF release, we used five different volume-expansion protocols in anesthetized dogs. A stepwise expansion of plasma volume (PV) was achieved by two consecutive infusions: 0.9% saline followed or preceded by 4 or 25% bovine serum albumin (BSA), 4 or 25% dextran (Dx), or homologous plasma. Saline expansion led to a two- to four-fold increase in arterial plasma ANF level in all five protocols. Both 4 and 25% BSA caused no or very modest increase in plasma ANF, while all other colloid expanders caused the expected ANF release. In all protocols, plasma ANF closely correlated with central venous pressure (CVP). BSA expansion was the only protocol with no correlation between PV and ANF release. Changes in serum Ca2+ could not explain this finding. During BSA expansion, the lack of atrial response was related to the absence of increment (or even fall) in CVP despite the expanded PV. Similarly, urinary Na+ excretion was correlated both with CVP and ANF level but not with PV in BSA expansion. When the dogs were depleted of histamine before BSA infusion, the atrial secretory response was restored, suggesting that this colloid was associated with augmented capillary leakiness and vascular fluid efflux. These results show that the expansion of PV leads neither to ANF release nor to Na+ excretion if it is not accompanied by an expanded central blood volume with elevated atrial pressure.Key words: atrial natriuretic factor, volume expansion, isotonic saline, bovine serum albumin, dextran, homologous plasma.
Effect of vasopressin on myocardial capillary recruitment and coronary blood flow in the anesthetized rabbit
Authors: Fuhr Walter , Russo Karen , Weiss Harvey R.
Published: April 2011

The effects of infusion of arginine vasopressin (20 mU∙kg−1∙min−1) on coronary blood flow and the proportion of the coronary microvasculature perfused was studied in rabbit myocardium. Fluorescein isothiocyanate – dextran was injected into anesthetized open-chest rabbits to identify the perfused vessels and an alkaline phosphatase stain was employed to locate the total microvasculature. Coronary blood flow (radioactive microspheres) was studied in separate groups of rabbits. Vasopressin infusion caused bradycardia (243 ± 19 to 165 ± 22 beats/min, mean ± SD) and an increase in mean blood pressure (92 ± 18 to 104 ± 12 mmHg) (1 mmHg = 133.32 Pa). Coronary blood flow decreased significantly with vasopressin from 209 ± 68 to 97 ± 36 mL∙min−1∙100 g−1. The proportion of the arteriolar bed per millimeter squared perfused decreased significantly after vasopressin from 54 ± 13 to 44 ± 21%, while the percentage of capillaries per millimeter squared increased significantly from 57 ± 6 to 67 ± 11%. There were no subepicardial versus subendocardial differences in any measured parameter. Thus, both coronary blood flow and the proportion of the arteriolar bed perfused decreased with vasopressin. However, compensation occurred in that the proportion of capillaries perfused increased. This indicated an independent level of control of the coronary arteriolar and capillary beds. These microvascular changes may help to maintain oxygen supply–demand balance with vasopressin in the heart.Key words: myocardial capillaries, arterioles, coronary blood flow, heart vasopressin, vasoconstriction.
Effects of hydroxyflutamide on rats treated with a superovulatory dose of pregnant mare serum gonadotropin
Authors: Yu Frank H. , Yun Young W. , Yuen Basil Ho , Moon Young S.
Published: April 2011

Immature female rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of the antiandrogen hydroxyflutamide on steroid production, particularly the biologically active androgens, in two experiments. In the first experiment, animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared with the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p < 0.05). Serum levels of testosterone and androstenedione, and their aromatized product 17β-estradiol, significantly decreased (p < 0.05) in the hydroxyflutamide-treated group; however, nonaromatizable androgen, 5α-dihydrotestosterone, was not affected. In the second experiment, ovaries obtained 48 h after stimulation with 4 or 40 IU PMSG were incubated with and without hydroxyflutamide (10−5 M) and (or) testosterone (10−7 M) to study [4-14C]pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p < 0.01) and androstenedione (p < 0.01), while the production of 17β-estradiol increased significantly (p < 0.05); however, pregnenolone conversions to testosterone and 5α-dihydrotestosterone were not affected. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in 4 IU stimulated ovaries. Present results confirm our previous finding that hydroxyflutamide decreases the percentage of abnormal oocytes recovered from superovulating rats and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis following inhibition of androgen binding in the ovary.Key words: superovulation, pregnant mare serum gonadotropin, antiandrogen, hydroxyflutamide, androgen.
The remodelling of skeletal muscle for indefatigable hemodynamic work
Authors: Odim J. N. K. , Li C. , Desrosiers C. , Chiu R. C.-J. , O'Brien P. J. , Hamilton N. , Ianuzzo C. D.
Published: April 2011

Skeletal muscle possesses inherent plasticity of gene expression. Low frequency pulse-train stimulation can remodel the biochemical machinery that confers physiological expression and fatigue resistance approaching that of the myocardium. This fatigue-resistant muscle can generate sufficient force to meet the power requirements for useful cardiac work. This ultimate goal is currently being pursued in models of cardiomyoplasty and muscle-powered cardiac assist devices. In this article, we review the three major subcellular systems subserving canine skeletal muscle transformation and compare them to those of cardiac muscle. The magnitude of the problem of clinical heart failure and the feasibility of fatigue-resistant skeletal muscle joining the therapeutic armamentarium are addressed. The adaptation and transformation of fast-twitch skeletal muscle in response to chronic electrical stimulation augers therapeutic potential as an endogenous, readily available power source for myocardial assistance. The basis mechanisms of skeletal muscle fatigue require elucidation to gain a complete and thorough understanding of how to manipulate this property to provide continuous hemodynamic work.Key words: muscle transformation, pulse-train stimulation, cardiomyoplasty, counterpulsation, cardiac assist, myosin isoforms, sarcoplasmic reticulum ATPase, myofibrillar ATPase.
Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation–contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure
Authors: O'brien Peter James , Shen Hua , Weiler Janice , Ianuzzo C. David , Wittnich Carin , Moe Gordon W. , Armstrong Paul W.
Published: April 2011

The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation–contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 ± 58 to 159 ± 57 nmol∙min−1∙mg−1 (mU/mg) and from 577 ± 82 to 177 ± 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 ± 2.4 to 3.11 ± 0.67 nM/s at 300 nM Ca and 38.7 ± 10.5 to 16.3 ± 8.0 nM/s at 1500 nM Ca, respectively (all p < 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p < 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration. In the pacing model Ca-ATPase activity and left ventricular diastolic area were correlated (r = −0.64), in the ischemia model Ca-ATPase activity was highly correlated with myocardial lactate concentration (r = −0.83) and acidity (r = −0.85) but not glycogen content, and in the malignant hyperthermia model Ca-sequestration activity was correlated with myocardial ionized Ca concentration (r = −0.63) (all p < 0.001). We conclude that failure of Ca sequestration by SR plays a major role in the pathogenesis of cardiac and muscle fatigue and failure owing to relative functional overload. A model is presented for the role of the SR in the pathogenesis of striated muscle fatigue.Key words: heart disease, fatigue, sarcoplasmic reticulum, Ca ATPase, Ca channel, malignant hyperthermia.
Effects of dynorphin A(1 – 13) and of fragments of β-endorphin on blood pressure and heart rate of anesthetized rats
Authors: Giersbergen Paul L. M. van , Lang Henk de , Jong Wybren de
Published: April 2011

The effect on blood pressure and heart rate of central administration of dynorphin A(1 – 13) and of β-, γ-, and α-endorphin related peptides was studied in urethane-anesthetized rats. Intracerebroventricular (i.c.v., 0.1 – 10 μg) administration of β-endorphin resulted in a dose-dependent, naltrexone-reversible hypotension and bradycardia. N-terminally modified fragments of β-endorphin did not reduce blood pressure and heart rate. On the other hand, a dose of 10 μg of β-endorphin(1 – 27), which lacks the four C-terminal amino acid residues of β-endorphin, induced a fall in blood pressure and had a biphasic effect on heart rate. These responses, however, were resistant to pretreatment with naltrexone. None of the fragments of β-endorphin smaller than β-endorphin(1 – 27) affected blood pressure when administered i.c.v. in a dose of 10 μg. A small transient bradycardia was observed after i.c.v. administration of 10 μg of β-endorphin(1 – 26), α-, and γ-endorphin. The naltrexone-reversible bradycardic response of α- and γ-endorphin was not present in des-tyrosine- and des-enkephalin-α- and γ-endorphin and also not in α-endorphin(10 – 16) and γ-endorphin(10 – 17). Upon i.c.v. administration (0.1 – 50 μg) a dose-dependent, naltrexone-reversible decrease in blood pressure and heart rate was induced by dynorphin A(1 – 13). The present data indicate a hypotensive influence of β-endorphin, β-endorphin(1 – 27), and dynorphin A(1 – 13), whereas other fragments of β-endorphin had little or no effect on the cardiovascular parameters investigated.Key words: β-endorphin fragments, blood pressure, heart rate, dynorphin A(1 – 13), anesthetized rats.