bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced chronotropic and inotropic responses of rat myocardium to cholinergic stimulus with aging
Authors: Su Na , Narayanan Njanoor
Published: April 2011

The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation. In this study, we determined the chronotropic and inotropic responses of the isolated, Langendorff-perfused hearts from adult (6–8 months) and aged (28–30 months) rats to cholinergic agonists so as to assess age-related alterations in postsynaptic cholinergic control of heart function. The results showed the following. (i) In isolated perfused spontaneously beating rat hearts, the negative chronotropic response to acetylcholine (10−9–10−5 M) was up to 4-fold greater in the aged compared with adult hearts; this age-related difference was less marked (2-fold) but not abolished in the presence of a maximally effective concentration (5 μM) of the cholinesterase inhibitor eserine. (ii) The cholinesterase-resistant agonist carbachol (10−9–2.5 × 10−6 M) elicited a 2- to 3-fold greater negative chronotropic response in the aged compared with adult hearts. (iii) In isolated perfused, electrically paced (4 Hz) rat hearts, carbachol (10−9–10−3 M) elicited a concentration-dependent negative inotropic response, which was 2-fold greater in the aged compared with adult heart at all carbachol concentrations, (iv) Acetylcholinesterase activities (micromoles per gram per hour) were 50–60% lower in the aged atria (83 ± 21) and ventricles (24 ± 6) than in adult atria (210 ± 20) and ventricles (47 ± 7). (v) No significant age-related difference was observed in the specific binding of (–)-[3H]quinuclidinyl benzilate to muscarinic receptor sites in atria or ventricles. These findings demonstrate a striking enhancement in the responses of the heart to cholinergic stimulus with aging, which can be attributed in part, but not solely to age-associated decline in cholinesterase activity. Age-associated alterations in muscarinic receptor linked events may also underlie the cholinergic hypersensitivity of the aging heart.Key words: aging, muscarinic receptor, cardiac performance in vitro, cholineresterase activity.
Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats
Authors: Mottola M. F. , Plust J. H. , Christopher P. D. , Schachter C. L.
Published: April 2011

The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague–Dawley rats. The exercise consisted of treadmill running at 30 m∙min−1, on a 10° incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth.Key words: age, exercise, pregnancy, glycogen storage patterns.
Use of high and low responders to novelty in rat studies on the role of the ventral striatum in radial maze performance: effects of intra-accumbens injections of sulpiride
Authors: Cools A. R. , Ellenbroek B. , Heeren D. , Lubbers L.
Published: April 2011

High and low responders to novelty (Wistar rats) were selected with the help of an open-field test and then equipped with intra-accumbens cannulae. They were then tested in a simple four-arm radial maze during 5 successive days, three trials per day, following intra-accumbens injections of distilled water or the dopaminergic D2 antagonist (±)-sulpiride. The injections were given 15 min before the first trial on each day. Both types of drug-naive rats reached the same level of performance on day 5. However, high responders made more visits, more revisits, and needed less time to make the first visit than low responders. Moreover, high responders showed their greatest increase in learning 2 days earlier than low responders. It is discussed that these differences between high and low responders are not due simply to differences in locomotor activity, but are due to a subtle, but important, difference in the mode of learning between both types. Sulpiride significantly attenuated the learning in both rat types; however, its effect in high responders was much less than that in low responders. It is suggested that the effects of sulpiride are not due to changes in locomotor activity, motivation, or perception, but are due to a learning deficit. The data are discussed in view of the genetic variation in the neurochemical and neurobiological makeup of the nucleus accumbens in both types.Key words: ventral striatum, radial maze, sulpiride, individual vulnerability.
Water and solute balance in rats during 10 h water deprivation and rehydration
Authors: Schoorlemmer Guus H. M. , Evered Mark D.
Published: April 2011

Rats with bladder and venous cannulas were deprived of water from midnight (00:00) to 10:00. Water deprivation reduced food intake within 2 h, reducing the amount of water sequestered in the gut and the solute load to the tissues. There was little change in either urinary water loss or osmolality, but water-deprived rats excreted more Na+, K+, and Cl− than food-matched controls. The change in solute balance helped preserve osmolality and cell volume at the expense of extracellular fluid volume. When water was returned, rats quickly drank enough to restore the intracellular but not the extracellular fluid deficit. Plasma osmolality and sodium concentration fell below predeprivation values. Urine osmolality and excretion of Na+, K+, and Cl− fell rapidly after drinking. Drinking continued at a slower rate for at least 4 h, but urine flow also increased so water balance stabilized. The changes in intake and electrolyte excretion during water deprivation and rehydration illustrate the important role of changes in solute balance in fluid homeostasis.Key words: water deprivation, thirst, drinking, water balance, sodium balance.
Characterization of a simple animal model for nonsteroidal anti-inflammatory drug induced antral ulcer
Authors: Wallace John L. , McKnight G. Webb
Published: April 2011

Most animal models of nonsteroidal anti-inflammatory drug (NSAID) induced gastric injury are characterized by acute, superficial erosions in the corpus region, whereas the clinically significant injury in man is the deep, antral ulcer. The purpose of this study was to characterize a model of NSAID-induced antral ulceration that more closely resembles the type of damage seen in man. Rabbits received indomethacin subcutaneously every 12 h. The progression of ulcer formation was followed by killing groups of animals after one to seven doses of indomethacin. The dose dependency of ulcer formation was assessed by giving indomethacin at doses of 1 to 20 mg/kg. Healing of antral ulcers was determined by examining the stomach at various times after administering the seventh dose of indomethacin (20 mg/kg). The effects of prophylactic treatment with misoprostol or ranitidine on ulcer formation were assessed. Indomethacin administration initially produced superficial erosions in the corpus and antrum, but with time, ulcers became apparent in the antrum. The formation of these ulcers was dependent upon the number of times indomethacin was administered and the dose. Similar ulcers could be induced with a second NSAID, diclofenac. Misoprostol treatment resulted in a significant reduction in the extent of indomethacin-induced antral ulceration, but ranitidine had no effect. Antral ulcers healed progressively following cessation of indomethacin administration and were almost completely resolved by 108 h after the final dose of indomethacin. These results demonstrate that subcutaneous NSAID administration to rabbits is a simple and reproducible method for producing ulcers that bear striking macroscopic resemblance to NSAID-induced antral ulcers in man. This model may be useful for studies of the pathogenesis of NSAID-induced ulcer and the factors that modulate the healing of these ulcers.Key words: gastric ulcer, nonsteroidal anti-inflammatory drug, prostaglandin, healing.
Shivering and nonshivering thermogenic responses of rats subjected to different patterns of heat acclimation
Authors: Sakurada Sohtaro , Shido Osamu
Published: April 2011

Male Wistar rats were divided into five groups: a control group kept at an ambient temperature of 24 °C for 14 days, and four heat-acclimated groups (two groups subjected to a constant ambient temperature of 33 °C for 4 days or 14 days (HC-14) immediately preceding the measurement; and another two groups subjected to an ambient temperature of 33 °C for about 5 h once a day for 4 days, or 14 days (HI-14) just prior to the measurement). After the completion of the schedule, the rats were placed in a temperature-controlled chamber. Hypothalamic (Thy) and interscapular brown adipose tissue (TBAT) temperatures, oxygen consumption [Formula: see text], and shivering activity were measured during a gradual fall in temperature of a water jacket surrounding the chamber (Tw) from 30 to 10 °C at a constant rate of 0.18 °C/min. During the fall in Tw, [Formula: see text] and TBAT increased significantly and shivering was induced without associate changes in Thy in all groups. Tw at the onset of a rise in metabolic heat production (onset of cold-induced thermogenesis) coincided with that at the onset of a rise in TBAT (onset of BAT thermogenesis), but was significantly higher than that at the onset of shivering. In HC-14 and HI-14 rats, Tws at the onset of cold-induced thermogenesis and BAT thermogenesis were significantly higher than those in control rats, whereas Tws at the onset of shivering were not different from those in control rats. The onset of cold-induced thermogenesis did not change after the 4-day heat exposure. These results suggest that heat exposure for 14 days, regardless of the pattern, shifts the lower critical temperature to a high level, and the changes are attributed to an upward shift in the ambient temperature at which nonshivering thermogenesis occurs.Key words: heat exposure, heat production, brown adipose tissue, lower critical temperature.
Prior glucose deprivation increases the first phase of glucose-induced insulin response: possible involvement of endogenous ATP and (or) ADP
Authors: Chapal J. , Bertrand G. , Hillaire-Buys D. , Gross R. , Loubatières-Mariani M. M.
Published: April 2011

A possible implication of endogenously released ATP and (or) ADP in insulin response to glucose stimulation was investigated in the isolated rat pancreas. The first phase of insulin response to the same glucose concentration (8.3 mM) was much higher in pancreas previously perfused in the absence of glucose than in pancreas previously perfused with 4.2 mM glucose. A P2 purinoceptor antagonist, 2,2′-pyridylisatogen tosylate, strongly reduced the higher first phase resulting from glucose deprivation; similarly, it reduced exogenous ATP-potentiated insulin response to a glucose increase from 4.2 to 8.3 mM. In contrast, 2,2′-pyridylisatogen tosylate did not modify the first phase of insulin response to 8.3 or 12.5 mM glucose in pancreas previously perfused with 4.2 mM glucose. Our results suggest that endogenous ATP and (or) ADP released in pancreatic islets in the absence of glucose could activate P2 purinoceptors and increase the magnitude of the first phase of insulin response to a glucose stimulation.Key words: glucose, insulin secretion, ATP, ADP, purinoceptors.
The release of somatostatin-14 from human submucosal ganglia in tissue culture
Authors: Accili E. A. , McIntosh C. H. S. , Buchan A. M. J.
Published: April 2011

A dispersed culture of cells from the submucous plexus of the human small intestine has been developed to examine the localization, release, and molecular characteristics of somatostatin immunoreactivity. Forty percent of the submucosal neurones per ganglion in tissue sections and 35% of cells per group of cells in culture contained somatostatin immunoreactivity. Acetic acid extracts of cultures contained 1990 ± 809 pg somatostatin immunoreactivity/106 cells. Incubation of cultures with phorbol 12-myristate 13-acetate (βPMA), an activator of protein kinase C, at concentrations up to 10−6 M for 120 min increased the release of somatostatin immunoreactivity by up to 23 times the basal level, and up to 27 times the basal level when extracellular K+ was increased from 5 to 10 mM. Of the total somatostatin immunoreactivity released in response to βPMA (10−6 M, 10 mM K+), 59% was present in the medium after 30 min and 80% after 60 min. Basal release of somatostatin immunoreactivity could be reliably measured only after 120 min. The release of somatostatin immunoreactivity by βPMA was not due to nonspecific membrane effects, since the inactive 4α-phorbol at the same concentrations did not alter basal release. Greater than 90% of somatostatin immunoreactivity present in acid extracts of cultures and released by βPMA eluted with the same retention time as synthetic somatostatin-14 on reverse-phase high-performance liquid chromatography.Key words: human enteric nerves, protein kinase C, human small intestine.
Essential fatty acid requirements in human nutrition
Authors: Innis Sheila M.
Published: April 2011

Arachidonic acid (20:4ω−6) and docosahexaenoic acid (22:6ω−3) are major acyl components of cell membrane phospholipids, and are particularly enriched in the nonmyelin membranes of the central nervous system. Dietary deficiency of linoleic acid (18:2ω−6) and linolenic acid (18:3ω−3) during development has been shown to result in reduced levels of 20:4ω−6 and 22:6ω−3 in the developing central nervous system, and this has been associated with altered learning behaviour and visual function. Synthesis of 20:4ω−6 and 22:6ω−3 depends on the dietary intake of 18:2ω−6 and 18:3ω−3, respectively, and the activity of the fatty acid desaturase–elongase enzymes. Oxidation of 18:2ω−6 and 18:3ω−3 for energy, or direct acylation of 18:2ω−6 into triglycerides, cholesteryl esters, and phospholipids, could also influence the amount of 20:4ω−6 and 22:6ω−3 formed. The tissue levels of 20:4ω−6 and 22:6ω−3, or other (ω − 6) and (ω − 3) fatty acids, compatible with optimum growth and development or health are not known. The amount of preformed 22:6ω−3 in the diet of adults, infants fed various milks or formulae, or animals is reflected in the circulating lipid levels of 22:6ω−3. Human milk levels of (ω − 6) and (ω − 3) fatty acids vary, depending in part on the mother's diet. A valid, scientific approach to extrapolate dietary essential fatty acid requirements from the composition of human milk or the circulating lipids of infants fed different diets has not been agreed on. Current data suggest that fatty acid requirements for development of term-gestation piglet brain and retina are met with 5.0% dietary kcal (1 cal = 4.1868 J) 18:2ω−6 and > 1.0% kcal 18:3ω−3, As in rodents and non-human primates, a diet source of 20:4ω−6 and 22:6ω−3 does not seem essential for the developing piglet central nervous system. However, studies in very premature infants suggest these infants may benefit from a dietary source of 20:4ω−6 and 22:6ω−3. Whether the low 20:4ω−6 and 22:6ω−3 status is due to oxidation of 18:2ω−6 and 18:3ω−3 for energy, the effects of early intravenous feeding with lipid emulsions, rapid growth, or immaturity of physiological or metabolic pathways in very preterm infants is not yet known.Key words: linoleic acid, linolenic acid, arachidonic acid, docosahexaenoic acid, brain, retina.
Zinc and selenium, site-specific versus general antioxidation
Authors: Bettger William J.
Published: April 2011

The essential nutrients zinc (Zn) and selenium (Se) provide an antioxidant function to animal cells by very different mechanisms. Se is an integral part of Se-dependent glutathione peroxidases, a group of water-soluble enzymes that catalyze the destruction of water-soluble and, in some cases, membrane-bound hydroperoxides. In dietary Se deficiency, Se-dependent glutathione peroxidase activities are decreased; at Se intakes above that which is required for optimal growth, there is a slight to moderate increase in Se-dependent glutathione peroxidase activities. Because of the enzymatic nature of the major role of Se as an antioxidant, Se can be categorized as having a general antioxidant function, controlling peroxide levels in cells by degrading hydroperoxides. On the other hand, Zn functions as an antioxidant only at specific sites, and is not a required cofactor for an antioxidant enzyme. Although Zn plays a structural role in the enzyme Cu,Zn superoxide dismutase, the activity of this enzyme is not decreased in Zn deficiency and its activity is usually depressed at high Zn intakes. Zn may function as a site-specific antioxidant by two mechanisms. Firstly, it competes with Fe and Cu for binding to cell membranes and some proteins, displacing these redox-active metals and making them more available for binding to ferritin and metallothionein, respectively. Secondly, Zn binds the sulfhydryl groups in proteins, protecting them from oxidation. Zn status does not directly control tissue peroxide levels but can protect specific molecules against oxidative and peroxidative damage.Key words: zinc, selenium, antioxidant, free radicals.
Isoproterenol antagonizes drug-induced prolongation of action potential duration in humans
Authors: Newman David , Dorian Paul , Feder-Elituv Randi
Published: April 2011

The effects of an isoproterenol infusion on the duration of the human right ventricular endocardial monophasic action potential at 90% repolarization were recorded in the absence and in the presence of an antiarrhythmic drag regimen containing class III effects in two similar groups of patients. The drugs used were amiodarone (N = 3, 300 ± 50 mg), sotalol plus quinidine (N = 11, 156 ± 13 mg sotalol, 1688 ± 594 mg quinidine), and sotalol alone (N = 3, 300 ± 20 mg). All patients had underlying coronary disease but no evidence of inducible ischemia. In the absence of antiarrhythmic drug, isoproterenol did not significantly change the relationship of action potential duration at 90% repolarization to cycle length; there was a linear decrease in action potential duration by 19.8% between a paced cycle length of 600 and 300 ms. Isoproterenol did not significantly shorten the action potential duration at any cycle length. However, isoproterenol decreased the ventricular effective refractory period at 400 ms drive from 240 ± 5.0 to 225 ± 6.0 ms (p < 0.05) accompanied by no change in the ratio of refractory period to steady-state action potential duration. In the presence of class III drug effects, the action potential duration was increased by an average of 9.2% at all paced cycle lengths longer than 300 ms (p < 0.05). The ventricular refractory period was increased from 240 ± 5 to 269 ± 9.0 ms (p < 0.05 compared with baseline) with a concomitant increase in the ratio of refractory period to action potential duration from 96 ± 2 to 103 ± 2% (p < 0.05 compared with baseline). With infusion of isoproterenol in the presence of a class III containing regimen, the drug-prolonged action potential duration was shortened (p < 0.05) by an average of 8.1% at all cycle lengths longer than 300 ms. These results suggest that isoproterenol simulation of enhanced sympathetic tone can antagonize drug prolongation of action potential duration and that in the absence of drugs, the effects of isoproterenol on the steady-state action potential duration are modest. The clinical utility of class III agents may be augmented by the addition of concomitant β-blockade.Key words: action potential duration, antiarrhythmic drugs, isoproterenol.
Characterization of endothelin receptors mediating contraction and relaxation in rabbit saphenous artery and vein
Authors: Auguet Michel , Delaflotte Sylvie , Chabrier Pierre-Etienne , Braquet Pierre
Published: April 2011

The endothelin receptors in rabbit isolated rings of saphenous artery and saphenous vein have been characterized using endothelin-1, endothelin-2, endothelin-3, sarafotoxin S6c, and BQ123. Although artery rings were more sensitive than those from vein to the contractile action of phenylephrine, endothelin-1 was about three times more potent as a contractile agonist on vein than on artery. In rings precontracted with phenylephrine, carbachol was 10 times more potent in vein than in artery rings to induce endothelium-dependent relaxation. However, in rings precontracted to a similar tone by endothelin-1, the relaxation elicited by carbachol was reduced in the vein but remained unchanged in the artery. In endothelium-denuded saphenous artery, endothelin-1 and endothelin-2 elicited contraction with equal potency, whereas endothelin-3 and sarafotoxin S6c were weak agonists. In saphenous vein, the rank order of sensitivity was sarafotoxin S6c > endothelin-2 > endothelin-1 = endothelin-3, whereas sarafotoxin S6c and, to a lesser extent, endothelin-3 act as partial agonists. The ETA receptor antagonist BQ123 shifted, to the right, the concentration–response curves of endothelin-1 on endothelium-denuded saphenous artery (pA2 = 7.25). In the endothelium-denuded saphenous vein, 10 μM BQ123 shifted to the right only the response to high concentrations of endothelin-1. In vein but not in artery, endothelin-1 and sarafotoxin S6c induced an endothelium-dependent relaxation, which was increased, in the case of endothelin-1, in the presence of BQ123. These results indicate that the rabbit saphenous vein contains a mixed population of ETA and ETB vasoconstrictor receptors located in the smooth muscle cells and vasorelaxant ETB receptors situated on endothelial cells. In contrast, the saphenous artery only possesses smooth muscle cell ETA receptors responsible for constriction.Key words: endothelium, endothelin, vein, artery, BQ123.
Uptake of organic anions by hepatocyte monolayers: codiffusion versus facilitated dissociation
Authors: Burczynski F. J. , Moran J. B. , Cai Z.-S.
Published: April 2011

We used the clearance ratio test to determine whether the presence of albumin enhances the uptake of palmitate by hepatocyte monolayers. If uptake is facilitated, then the ratio of palmitate clearance by hepatocytes in the presence of 600 and 300 μM albumin (i.e., [Formula: see text]) will exceed the square root of the ratio of the unbound fractions at 600 and 300 μM albumin (i.e., [Formula: see text]). The latter value was determined using the heptane–water partitioning technique. The hepatocyte clearance ratio (0.92 ± 0.06) exceeded the predicted value (0.80) by 15% (p < 0.05). The observed clearance rate also exceeded that predicted by the diffusion–reaction model.Key words: hepatocytes, albumin, diffusion, clearance, palmitate.
Two sites of action for LCB29 (idrocilamide) in depressing mechanical tension of rat soleus muscle fibers?
Authors: Mouzou Aklesso , Bouron Alexandre , Guillemain Joel , Guerrier Daniel , Raymond Guy
Published: April 2011

The effects of 50 μM LCB29 (idrocilamide) were tested on depolarization-induced and caffeine contractures of rat soleus muscle fibers. When applied intracellularly by free diffusion in cut-end voltage-clamped fibers, LCB29 decreased tension amplitude by about 25%. The same amount of inhibition by LCB29 was observed on contractures induced by 6 mM caffeine. The drug did not affect the repriming of caffeine contractures, indicating that internal recycling of calcium was not affected. The voltage-dependent inactivation of tension was facilitated by external application of LCB29. This effect was calcium dependent, so that the greater the external calcium concentration, the greater the drug effectiveness. The spontaneous relaxation of K+ contractures was also accelerated by LCB29. It is concluded that LCB29 acts intracellularly by decreasing sarcoplasmic reticulum calcium release and externally by facilitating the voltage-dependent inactivation of the voltage sensor for excitation–contraction coupling.Key words: myorelaxants, skeletal muscle, sarcoplasmic reticulum calcium release, voltage sensor.
Increase in plasma thyroid hormone levels during the previous heat exposure time in heat-acclimated rats
Authors: Shido Osamu , Sakurada Sohtaro , Hashimoto Takuma , Fujikake Kazumi , Nagasaka Tetsuo
Published: April 2011

The present study was conducted to investigate day–night variations of plasma thyroid hormone and energy substrate levels in rats after acclimation to heat loaded for several hours at a fixed time per day. The heat-acclimated rats were exposed to an ambient temperature of 33 °C for 5 h in the last half of the dark phase for 16 consecutive days, while the control rats were kept at 24 °C for the same period. After completing the schedule, plasma levels of triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), cortisol, triglyceride, nonesterified fatty acid, total protein, and glucose were measured at 3-h intervals between 00:00 and 18:00 (dark phase, 03:00–15:00). The plasma levels of T3 and FT3 of the heat-acclimated rats were higher than those of the controls in the last half of the dark phase. Similar differences were observed for T4 and FT4 levels. The plasma cortisol level was consistently higher in the heat-acclimated rats than in the control rats. There were no particular differences in energy-substrate levels between the two groups at any time of the day. These results indicate that heat exposure at a fixed time per day alters the pattern of day–night variations of plasma thyroid hormone levels in rats. It is noteworthy that the plasma levels of thyroid hormones, especially T3 and FT3, increased during the period when the rats had been previously exposed to heat.Key words: triiodothyronine, thyroxine, cortisol, energy substrate, circadian rhythm.
Investigation of α1-adrenoceptor subtypes in canine aorta, using alkylating agents
Authors: Hoo K. H. , Kwan C.-Y. , Daniel E. E.
Published: April 2011

The ability of putative selective irreversible ligands SZL-49 (1-(4-amino-6,7-dimethyoxy-2,5-diene-2-carbonyl)) and CEC (chlorethylclonidine), for α1A and α1B adrenoceptor subtypes, respectively, to affect α1-adrenoceptors of canine aorta microsomal membranes was investigated. These membranes contain an apparently homogeneous population of [3H]prazosin binding sites. SZL-49, like phenoxybenzamine, abolished all binding of [3H]prazosin. CEC abolished 75% of the prazosin binding sites under the most stringent conditions we applied. However, the remaining 25% of binding sites was identical in affinity for prazosin with control membranes, and competition studies of other subtype-selective ligands revealed unchanged ability to compete against CEC-sensitive and -insensitive sites. We concluded that SZL-49 and CEC are not α1A- and α1B-adrenoceptor selective under in vitro conditions. Our data led to the hypothesis that canine aortic membranes contain exclusively α1B-adrenoceptors but that current tools for identifying α1-adrenoceptor subtypes proved inadequate in vitro in this study.Key words: chlorethylclonidine, WB4101, SZL-49, prazosin, rauwolscine.
Elevated muscle citrate does not reduce carbohydrate utilization during tetanic stimulation
Authors: Dyck David J. , Spriet Lawrence L.
Published: April 2011

The purposes of this study were to determine whether enhanced free fatty acid delivery would result in increased muscle citrate levels and to establish whether the effects of this putative phosphofructokinase inhibitor would be manifested during intense stimulation demanding glycogen as a fuel. Hind-limb muscles were perfused with either no or high (0.93 ± 0.03 mM) free fatty acids for 10 min at rest, and during 5 min of tetanic stimulation. Muscles sampled at the end of the rest perfusion or stimulation were soleus (slow oxidative), red gastrocnemius (fast oxidative glycolytic), and white gastrocnemius (fast glycolytic). Muscle citrate content was unaffected during rest perfusion with no free fatty acids, whereas high free fatty acids significantly elevated citrate above control in soleus, red gastrocnemius, and white gastrocnemius (by 0.39 ± 0.13, 0.53 ± 0.10, and 0.29 ± 0.07 μmol∙g−1 dry muscle, respectively). Following 1 min of stimulation, citrate content in soleus and red gastrocnemius was not different from control in the absence of free fatty acids but accumulated significantly with high free fatty acids (0.26 ± 0.05 and 0.28 ± 0.04 μmol∙g−1 dry muscle, respectively). Following 5 min of stimulation, soleus and red gastrocnemius citrate content decreased with no free fatty acids but increased significantly with high free fatty acids (0.42 ± 0.10 μmol∙g−1 dry muscle) in soleus and remained unchanged in red gastrocnemius. The presence of high free fatty acids had no effect on glycogen utilization or lactate accumulation in stimulated soleus and red gastrocnemius, or stimulated white gastrocnemius citrate, glycogen, or lactate contents. In addition, no effect of elevated free fatty acids on resting or stimulated muscle glucose-6-phosphate content, glucose uptake, or lactate efflux was observed. In conclusion, the elevation of muscle citrate due to the presence of free fatty acids in the perfusate did not reduce muscle glycogenolysis when the demand for energy was great.Key words: citrate glycolysis, phosphofructokinase, glycogen.
Indirect hypertensive actions of long-term intracarotid angiotensin II infusion during ovine pregnancy
Authors: Mukaddam-Daher S. C. , Aberdeen G. W. , Cha S. C. , Gutkowska J. , Nuwayhid B. S. , Quillen Jr. E. W.
Published: April 2011

Angiotensin II (AngII) influences the regulation of mean arterial pressure (MAP) through numerous mechanisms, including an action of circulating AngII on the brain to alter autonomic activity. We have obtained evidence that the relative importance of this effect is increased during pregnancy. Consequently, these studies were undertaken to assess the effects of bilateral infusion of AngII (0.35 ng∙kg−1∙min−1∙artery−1) into the internal carotid arteries (ica) of sheep for 13 days. Six nonpregnant (NP) and six 105- to 125-day pregnant (PG) ewes were maintained in large metabolism cages, where MAP was continuously monitored. By day 10 of ica AngII infusion in NP ewes, MAP was increased from 83.9 ± 1.6 to 92.9 ± 2.8 mmHg (1 mmHg = 133.3 Pa) (p = 0.001). Twenty-four hour urine volume (UV, 2664 ± 341 to 1583 ± 228 mL; p = 0.005) and sodium excretion (UNaV, 190 ± 5 to 113 ± 19 mmol/day; p = 0.005) were decreased. 51Cr-tagged blood volume (BV) was increased on day 13 (3643 ± 187 to 4379 ± 446 mL; p = 0.05). In contrast, by only day 6 of ica AngII infusion in PG ewes, MAP increased from 79.1 ± 1.9 to 84.1 ± 1.4 mmHg (p = 0.03) in association with a BV expansion from 3999 ± 274 to 4207 ± 275 mL. These changes were preceded by decreases in UV (2813 ± 413 to 2198 ± 362 mL; p = 0.01) and UNaV (190 ± 15 to 118 ± 26 mmol/day; p = 0.01). By day 13, MAP had plateaued at 93.0 ± 1.2 mmHg. There were no changes in plasma AngII, plasma renin activity, arginine vasopressin, and atrial natriuretic factor during ica AngII infusion in either NP or PG ewes, suggesting that these effects are mediated via the central nervous system. Moreover, the data suggest that MAP is increased secondary to volume expansion associated with sodium and water retention. This effect appears to be more readily exhibited during pregnancy. Furthermore, this study demonstrates the importance of the rennin–angiotensin system in blood pressure homeostasis by actions other than direct vasoconstriction.Key words: angiotensin II, blood pressure, hypertension, sheep, pregnancy, sodium balance.
Electrophysiologic properties of a narrow isthmus in rabbit atrial tissue: cycle length dependent effect of quinidine
Authors: Qi Anzhen , Kerr Charles R. , Yeung-Lai-Wah John A.
Published: April 2011

The modulation of quinidine's effect by pacing cycle lengths was assessed over an isthmus of atrial myocardium, simulating the Wolff-Parkinson-White syndrome. Isolated rabbit atria were dissected so that two tissue blocks, A and B, were linked by an isthmus, 1 mm in width. Effective refractory period in the tissue blocks and over the isthmus was measured at cycle lengths of 1000, 600, and 400 ms, and the minimum cycle length to sustain 1:1 conduction over the isthmus was measured before treatment, during quinidine superfusion (4 mg/L), and after washout. Longitudinal velocity over the isthmus was also measured. The increment in the effective refractory period in the tissue blocks by quinidine appeared to be similar, about 10% at three pacing cycle lengths (p > 0.05). However, the increment of the effective refractory period over the isthmus was modulated by pacing cycle lengths: greater increase at shorter cycle lengths (p < 0.001). Quinidine prolonged the minimum cycle length over the isthmus by 44 ± 17%. Regression analysis showed that after quinidine there was a correlationship between conduction velocity and refractoriness over the isthmus (R = 0.85, p < 0.001). Intracellular impalements showed stable action potentials, confirming the integrity of the preparation. We conclude that (i) quinidine preferentially prolongs refractoriness over the isthmus and (ii) quinidine's effect on refractoriness over the isthmus is cycle length dependent.Key words: atrial action potential, conduction velocity, quinidine, refractory period.
In vivo magnetic resonance imaging study of Kupffer cell involvement in CCl4-induced hepatotoxicity in rats
Authors: Towner Rheal A. , Reinke Lester A. , Janzen Edward G. , Yamashiro Shigeto
Published: April 2011

When carbon tetrachloride (CCl4) was administered to rats, a localized region of hepatic edema could be detected within 1 h by in vivo proton magnetic resonance imaging. However, if rats were pretreated with gadolinium chloride (GdCl3), an inhibitor of Kupffer cell function, the CCl4-induced edema was greatly decreased. Methyl palmitate, another Kupffer cell inhibitor, also decreased the degree of edema caused by the administration of CCl4. Electron micrographs of samples that were taken from regions of the liver where the edema was localized indicated formation of vacuoles and lipid droplets in parenchymal cells and enlargement of Kupffer cells, which exhibited numerous phagosomes and extensive pseudopod formation. These electron micrograph changes were also attenuated by pretreatment of the rats with GdCl3 and methyl palmitate. In vivo spin trapping and electron paramagnetic resonance experiments indicated that GdCl3 did not affect the metabolism of CCl4 to the trichloromethyl radical. The data in this report suggest that localized hepatic edema which occurs soon after administration of CCl4 involves activation of Kupffer cells, and that trichloromethyl radical production may be a separate but related process occurring in parenchymal cells. These observations support reports from other laboratories that Kupffer cells may be involved in CCl4-induced hepatotoxicity.Key words: carbon tetrachloride, hepatotoxicity, magnetic resonance imaging, gadolinium chloride, Kupffer cells.
Active versus passive touch: factors influencing the transmission of somatosensory signals to primary somatosensory cortex
Authors: Chapman C. Elaine
Published: April 2011

Active and passive touch, respectively with and without voluntary movement on the part of the subject, are frequently reported to be equivalent in terms of the resultant perceptual abilities. This review reexamines the notion of perceptual equivalence in the light of growing evidence that the transmission of tactile inputs is diminished, or "gated," during the course of active movement. It is concluded that there is indeed gating of cutaneous inputs during active touch. In most experiments, the paradoxical observation of perceptual equivalence between active and passive touch can partly be explained by the choice of task, namely, tactile discriminations that depend on relative, and not absolute, differences in inputs. The surprising lack of evidence for any superiority of passive touch over active touch can likely be explained by several factors. First, performance with active touch may be enhanced by the motor strategy, e.g., by reducing the speed of movement at critical points, and so reducing the degree of gating, and (or) by optimally orienting the exploring digits so as to bring the most sensitive skin areas into contact with the object in question. Second, central influences, including attention and motor set, may be specifically activated during voluntary movement and contribute to enhancing performance during active touch. Thus, the gating influences associated with active touch may be offset, partly or wholly, by the combined influence of these factors to yield (near) perceptual equivalence for active and passive touch.Key words: cutaneous, gating, somatosensory evoked potentials, movement, somatosensory discrimination.
Cation fluxes and cation channels in outer segment membranes of bovine retinal rods: contamination by antibiotics applied to cattle?
Authors: Lopez-Escalera Ricardo , French Robert J. , Schnetkamp Paul P. M.
Published: April 2011

Membrane vesicles were prepared from intact rod outer segments (ROSs) isolated from bovine retinas and were examined for the presence of cation-selective conductances. We performed macroscopic flux measurements in an ensemble of ROS membrane vesicles and single-channel measurements after fusion of ROS membrane vesicles with planar bilayer membranes. Two K+-permeable conductances were observed, the well-established cyclic GMP (cGMP) gated channel and an apparently new K+ channel with some unusual properties. Flux and single-channel data showed that the new conductance passed K+, Rb+, and Cs+ equally well but was much less permeable to Na+, Li+ and protons. Single-channel measurements revealed a linear current–voltage relationship and three unitary conductance states of 15, 11, and 8 pS, using symmetric 150 mM KCl solutions. Measured macroscopic K+ fluxes varied considerably among different preparations, suggesting some unknown regulation of the channel; the variability appeared to arise from variation in the channel's open probability, not the unit conductance or the number of channels present. The recorded single-channel events and the selectivity data are remarkably similar to those reported for antibiotic channel-forming ionophore gramicidin. We believe that the variability in both macroscopic permeability experiments and single-channel experiments may reflect a variable contamination with gramicidin applied to the animals as the topical antibiotic V-Sporin.Key words: cyclic GMP gated channel, ion channel, rod photoreceptor, gramicidin.
Substance P activates Cl− and K+ conductances in guinea-pig tracheal smooth muscle cells
Authors: Janssen Luke J. , Sims Stephen M.
Published: April 2011

Substance P (SP) causes bronchoconstriction, but its effects on airway smooth muscle ion conductances are unknown. We investigated the effects of SP on single smooth muscle cells dissociated from guinea-pig trachealis. Under voltage clamp at −60 mV, SP evoked reversible contractions and inward current (ISP). ISP had a latency of approximately 1 s, reached a peak of 1039 ± 147 pA (n = 19) about 2 s after onset of application, and declined to baseline levels over the next 5–10 s. At more positive holding potentials (−25 and 0 mV), the inward current was decreased in magnitude and preceded by outward current. With 140 mM K+ in the electrode and Cl− equilibrium potential (ECl) of about 0 mV, ISP was outwardly rectifying and reversed at −11 ± 2 mV. When K+ currents were blocked using Cs+, the current–voltage relationship for ISP was linear and reversed at 3 ± 1 mV. The reversal potential was dependent on the Cl− gradient across the membrane. These results suggest that SP caused a transient activation of Cl− and K+ conductances. Following the initial transient inward current, SP caused a prolonged suppression of spontaneously active K+ currents. The findings that SP evoked contractions during voltage clamp at potentials at which voltage-dependent Ca2+ channels are not active, and that current oscillations were also evoked by SP, suggest that SP is acting through release of Ca2+ from internal stores. Furthermore, SP occluded the inward current evoked by acetylcholine, suggesting that the peptidergic and cholinergic signalling pathways converge. We conclude that SP releases Ca2+ from internal stores in guinea-pig airway smooth muscle cells, leading to activation of Cl− and K+ conductances, depolarization, and contraction.Key words: Ca2+-dependent conductances, spontaneous transient outward currents, acetylcholine.
Uterine vascular permeability after uterine stimulation to rats differentially sensitized for the decidual cell reaction
Authors: Hamilton G. S. , Kennedy T. G.
Published: April 2011

Uterine vascular permeability (VP) was assessed after unilateral intrauterine injection of sesame oil to rats given either optimal sensitization for the decidual cell reaction or one of several forms of suboptimal sensitization. The study was intended to determine the relationship between changes in uterine VP and imminent endometrial decidualization. Uterine VP was estimated by the rate at which the uterine volume of distribution of i.v. injected, 25I-labeled albumin approached the uterine extracellular fluid volume (ECFV). When ideal sensitization was provided, uterine VP was significantly greater in stimulated than nonstimulated horns at 4, 8, 16, and 32 h after stimulation (p < 0.05). Maximum VP in stimulated horns occurred at 8 h, with the time for the 125I-labeled albumin volume to reach half the uterine ECFV (t1/2) estimated to be 30 min. Different types of sensitization resulted in different levels of uterine VP in stimulated and nonstimulated horns, with maximal VP occurring in stimulated horns of rats that had previously received optimal sensitization for decidualization. We conclude that endometrial decidualization is preceded by significant increases in uterine VP and that optimal sensitization promotes an optimal VP response.Key words: decidualization, vascular permeability, rats.
Pyridostigmine bromide does not alter thermoregulation during exercise in cold air
Authors: Roberts Donald E. , Sawka Michael N. , Young Andrew J. , Freund Beau J.
Published: April 2011

This study examined the effects of acute and chronic pyridostigmine bromide (PB) administration on thermoregulatory and metabolic responses to exercise in cold air (5 °C). Seven healthy men completed two 7-day trials in a double-blind, crossover experimental design: during one trial they received PB (30 mg three times daily) and during the other trial they received placebo. For each trial, subjects attempted four (3 h) exercise tests: low-intensity exercise (~ 25% [Formula: see text]) and moderate-intensity exercise (~ 50% [Formula: see text]), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body temperatures, and venous blood samples were obtained before and during exercise. Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05) from 34% on day 1 to 43% on days 3–7. Metabolic rate, body temperatures, and regional heat conductance responses were not different between trials. Plasma glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations were not different between trials. In addition, differences were not found between acute and chronic experiments for any thermoregulatory or metabolic responses. These findings demonstrate that the PB dosage used by military personnel, as a pharmacological defense against nerve-agent poisoning, should not cause any adverse thermoregulatory or metabolic effects during moderate activity in cold climates.Key words: anticholinesterase, cold-induced vasoconstriction, cold-induced thermogenesis, cold stress, insulative shell, body temperature regulation.
Effect of cyclopiazonic acid on contractile responses in slow and fast bundles of cremaster skeletal muscle from the ferret
Authors: Huchet Corinne , Léoty Claude
Published: April 2011

The effects of cyclopiazonic acid (CPA) on twitch force, calcium (Ca2+) uptake and release by the sarcoplasmic reticulum (SR), and Ca2+ sensitivity of contractile apparatus were studied using intact and chemically skinned cremaster fibers and compared with those on the extensor digitorum longus and soleus. In cremaster muscles treated with CPA (0.5–5 μM) a potentiation of the twitch was observed, associated with an increase in time to peak and in time of relaxation. In Triton-skinned fibers, CPA, at concentrations less than 10 μM, exerted no significant effect on the contractile apparatus of either slow- or fast-twitch fibers. In slow-twitch fibers, a dose-dependent increase in Ca2+ sensitivity was associated with a decrease in maximal tension, at CPA concentrations > 10 μM. In saponin-skinned fibers, during the uptake phase, CPA at > 10 μM induced a dose-dependent decrease in caffeine contracture. The possibility of an action on the SR Ca2+ release channel was excluded by testing the effect of CPA during the releasing phase. The enhancing effect of CPA (0.5 – 5 μM) on mechanical activity could be explained by an inhibition of the SR Ca2+ ATPase in skeletal muscle cells without an effect on the contractile proteins. Our results strongly suggest that CPA (< 10 μM) has a highly specific effect on the SR Ca2+ pump in the fast- and slow-twitch fibers and therefore could be a good tool to study the mechanisms of Ca2+ regulation in skeletal muscles. Furthermore, the study of the SR properties, using CPA, has shown no significant differences in the SR function of ferret cremaster fibers in comparison with extensor digitorum longus and soleus muscles.Key words: caffeine, skinned fiber, sarcoplasmic reticulum.
Effects of vanadium treatment on the alterations of cardiac glycogen phosphorylase and phosphorylase kinase in streptozotocin-induced chronic diabetic rats
Authors: Liu Heyi , McNeill John H.
Published: April 2011

Supersensitivity to isoproterenol (ISO) induced activation of cardiac phosphorylase in diabetic rat heart has been previously demonstrated and was also reproduced in this study. To explore further the nature of this supersensitivity, we examined the activity of phosphorylase kinase and the level of cyclic AMP (cAMP) in this tissue. We observed a significantly enhanced activation of phosphorylase kinase but no increase in cAMP levels in response to ISO stimulation in diabetic rat heart, suggesting that the supersensitivity of phosphorylase activation in diabetic heart may result from an enhanced activation of phosphorylase kinase that does not involve the cAMP pathway. On the other hand, perfusion of diabetic rat heart with verapamil (5 × 10−8 M) prior to ISO stimulation abolished the enhanced cardiac phosphorylase activation, suggesting a role for calcium in the supersensitivity of phosphorylase activation. Furthermore, treatment of the diabetic rats with an insulin-like compound, vanadyl sulphate, completely abolished the enhanced cardiac phosphorylase activation and restored the increase in ISO-induced cAMP elevation in diabetic heart. The present study has provided further information on the changes of phosphorylase activation in the diabetic rat heart and demonstrated beneficial effects of vanadyl sulphate on the pathway leading to phosphorylase activation in diabetic rat heart.Key words: phosphorylase, phosphorylase kinase, catecholamines, vanadium.